REACTION INTERMEDIATES &

MECHANISM

Presented ByJasmeen QuadirKV No. 3Bhopal

Most of the organic reaction occur through the involvement of certain chemical species. These are generally short – lived (10-6 second to a few second ) and highly reactive and hence cannot be isolated. These short –lived highly reactive chemical species through which the majority of the organic reactions occur are called reactive intermediates.

Some examples of reaction intermediates are:Carbocations, Carbanions, Free- radicals, Carbenes, Nitrenes.

Reaction Intermediates

Carbocations

Chemical species bearing a positive charge on carbon and carrying six electrons in its valence shell are called carbocations or carbenium ions.

By heterolytic cleavage of the covalent bonds in which the leaving group takes away with it the shared pair of electrons (of the covalent bond). For example.

(CH3)3C ─ Cl → (CH3)3C+ + Cl-

tert –Butyl chloride tert –Butyl carbocation

Stability

The stability of carbocations follow the order -

3° > 2° > 1° > methyl.

This order of stability can be explained on the basis of the following factors:

(a) Inductive Effect

(b) Resonance Effect

(c) Hyperconjugation Effect

(a)Inductive effect More the number of alkyl group on the carbon atom carrying the +ve charge, greater would be the dispersal of the charge and hence more stable would be the carbocation. Thus, the stability of the carbocations decereases in the order: 3°> 2°> 1°> ;

C+R

R

R

30

C+R

R

H

20

C+R

H

H

10

C+H

H

H

Methyl carbocation

> > >

Stability decreases as +I-effect of the alkyl group decreases

(CH3)C > CH3CHCH3 > CH3CH2CH2 > CH3CH2 > CH3+++ + +

(b) Resonance effectCarbocations in which the +vely chared carbon atom is attached to a double bond or a benzene ring are stabilized by resonance.

CH2 CH ─ CH2 ↔ CH2 ─ CH CH2

(Allyl carbocations is stabilized by resonance)

++

More the number of phenyl group, greater is the stability.

(C6H5)3C+ > (C6H5)2CH+ > C6H5CH2

+

(c)Hyperconjugation effectTert – Butyl carbocation has nine α-hydrogens and hence nine hyperconjucation structures.

H H C C CH3

H C H3

+

H+

H C C CH3

H CH3

H H+

C C CH3

H CH3

H H C

C CH3

H+ CH3

The stability of the various carbocations decreases in the order:

(C6H5)3C+ > (C6H5)2CH+ > (CH3)3C

+ > C6H5CH2+ >

(CH3)2CH+ > CH2 = CH ─ CH2+ > RC = CH2 > CH3CH2

+ >

RCH = CH+ > C6H5+ > CH3

+ > HC ≡ C+

+

ReactivityThe order of reactivity of any chemical species is reverse that of its stability. Therefore the order of reactivity of carbocations follow the sequence: 1°> 2°> 3°>

Orbital structureThe three sp2-hybridized orbitals of this carbon form three σ-bonds with monovalent atoms or groups lie in a plane are inclined to one another at an angle of 120°.

C+1200

R

R

Rsp2 – HYBRIDIZED CARBON

EMPTY p-ORBITAL

Orbital structure of carbocations

Carbanions Chemical species bearing a negative charge on carbon and possessing eight electrons in its valence shell are called carbanions,

HO- + H ─ CH2 ─ CHO → H2O + CH2 ─ CHOHydroxide ion Acetaldehyde ion Acetaldehyde carbocation

-:

H2N- + H─ C≡C ─ H → NH3 + C≡C─H

Amide ion Acetylene

Stability

(a)Inductive effectThe stability of simple alkyl carbanions follow the order:

CH3- > 1°> 2°> 3°.

> > >C:-H

H

H

Methyl carbonion

C:-R

H

H

10

C:-R

R

H

20

C:-R

R

R

30

(b) Resonance effect Allyl and benzyl carbanions are stabilized by resonance.

CH2 CH ─ CH2 ↔ -CH2 ─ CH CH2 (Allyl carbanion is stabilized by resonance)

-

:CH2- CH2

:-

CH2

: -

CH2

-:

:CH2-

(Benzyl carbanion is stabilized by resonance)

(C6H5)3C- > (C6H5)2CH- > C6H5CH-2

(c)s- CharacterStability of the carbanion increases with the increase in s- character of the carbon carrying the –ve charge.

R ─ C ≡ C- > R2C = CH- > R ─ CH2-

50% s- character 25% s- character33% s- character

ReactivityThe order of reactivity of carbanions is reverse of the order of stability, 30 > 20 > 10 > CH-

3

Orbital structureThe structure of simple alkyl carbanions is usually pyramidal just like those of ammonia and amines. The carbon atom carrying the negative charge is sp3-hybridized. Three of the four sp3-hybridized orbitals form three -bonds with monovalent atoms or group while the fourth sp3 –orbital contains the lone pair of electrons.

The carbanions which are stabilized by resonance are planar. In these carbanions, the carbon atom carrying the –ve charge is sp3 – hybridized.

Thus, whereas (CH3)3C- is pyramidal, allyl carbanion is planar.

Orbital structure

C-

Orbital structure of carbanions

R

R

R

. .

sp3 – HYBRIDIZED CARBON

sp3 - ORBITALLONE PAIR

Free Radical A free radical may be defined as an atom or a group of atoms having an odd or upaired electron .

Cl ─ Cl Cl ─ Cl hv or

Homolytic cleavageChlorine free radicalsChlorine

Classification

R ─ CH2

Primary (10)

R R ─ CH2

Secondary (20)

R R ─ C ─ R

Tertiary (30)

Stability The order of stability of free radicals is the same as that of carbocations. 3°> 2°> 1°>.

CH3

CH3 ─ C ─ CH3

tert – Butyl free radical (30)

CH3

CH3 ─ CH

Isopropyl free radical (20)

CH3 ─ CH2

Ethyl free radical (10)

CH3Methyl free radical

>> >

The stability of the various free radicals in the order.

(C6H5)3C > ( C6H5)2CH > C6H5CH2 >

CH2=CH─CH2 > (CH3)3C > (CH3)2CH >

CH3CH2 > CH3 > CH2=CH > HC≡C

Orbital structure Alkyl free radical like carbocations are planar chemical species. The only difference being that in carboctions, the unhybridized p-orbital is empty while in the free radical, it contain the odd electron.

C1200

R

R

Rsp2 – HYBRIDIZED CARBON

p-ORBITAL

Orbital structure of free radicals

. UNPAIRED ELECTRON

Mechanisms of nucleophilic substitution reaction

There are two type of nucleophilic substitution reaction:

(i) SN1 Mechanism (unimolecular nucleophilic substitution)

(ii) SN2 Mechanism (Bimolecular nucleophilic substitution)

IN this type, the rate of reaction depends only on the substrate (i.e., alkyl halide) and the reaction id of the first order change.

Rate [Substrate] or Rate = k [RX]

(i) SN1 Mechanism (unimolecular nucleophilic substitution)

THIS TYPE OF REACTION PROCRRDS IN TWO STEP AS:

STEP 1. The alkyl halide undergoes heterolytic fission forming an intermediate, carbocation. This step is slow and hence is the rate determining step of the reaction.

Slow step

CH3

CH3 C+ X-

CH3

Carbocation

CH3

CH3 C X CH3

Tert. butyl halide

R ―X R+ + X- Slow step Carbocation

STEP 2. The carbocation ion being a reactive chemical

species, immediatrly reacts with the nucleophile [:Nu- ] to give the substitution product. This step is fast and hence does not affect the rate of reaction.

CH3

CH3 C OH CH3

Tert. butyl alcohol

R +― :Nu- R ― Nu Fast step

CH3

CH3 C+ + OH-

CH3

Tert. butyl carbocation

Nucleophile

If the alkyl halide is optically active, then the product is a racemic mixture.

Thus, racemization occurs in SN1 reactions. The order of reactivity depends upon the stability of carbocation formed in the first step. Due to stable nature of 3° carbocation, the SN

1 reaction is favored by heavy (bulky) group on the carbon atom attached to halogens.

and nature of carbocation in substrate is:

SN1 Order:

Benzyl > allyl > 30 > 20 > 10 > methyl halides

R3C ― X > R2CH ― X > R ― CH2 ― X > CH3 ― XTertiary (30)

Secondary (20)

Primary (10)

(ii) SN2 Machanism (Bimolecular nucleophilic subsititution):

In This type, the rate of reaction depends on the concentration of both substrate (alkyl halide) and the nucleophilic; the reaction is said to be SN

2 , the second order change

Rate [Substrate] [Nucleophile] or

Rate = k [ RX ] [ :Nu- ]

Hydrolysis of methyl chloride is an example of SN2 reaction

and high reaction concentration of the nucleophile (OH-) favours SN

2 reaction. The chlorine atom present in methyl chloride is more electronegative than the carbon atom.

Therefore C ― Cl bond is partially polarized.

H H C+ Cl -

H

When the methyl chloride is attacked by OH- strong nucleophile from the opposite side of the chlorine atom, a transition state results in which both OH and Cl are partially bonded to carbon atom. H O C Cl H

H

H

- -

HO- - - - - -C- - -- - - Cl H

H H

Transition state

H

HO C H + Cl- H

Alcohol

SN2 reaction of optically active halides are concerted reactions

and configuration of carbon is changed. This process is called as inversion of configuration, complete inversion takes place. This inversion of configuration is commonly known as Walden Inversion.

Nu- + R X [Nu ------- R -------- X] Nu R + X - Slow Fast

Transition state

H O CCH3

n – C6H13

(+) Octan – 2 – ol

H + Br-H O +

-C Br

H3C

n – C6H13

(–) -2 - Bromooctane

H

CH3 X > RCH2 X > R2CH X > R3C X Primary Secondary Tertiary

SN2 order :

Methyl > 10 > 20 > 30 > allyl > benzyl halides

The nature of carbocation in substrate is :

MECHANISM OF

HALOGENATION

Halogenation of benzene is an electrophilic subsititution reaction.

Cl ― Cl + FeCl3 → Cl+ + Fecl-4(Electrophile)

Step 1. The electrophilic, i,e., halonium ion (Cl+, Br+ or I+) is generated by the action of Lewis acid (FeCl3 or anhyd. AlCl3........etc.) on the halogens.

Step 2: The electrophile (Cl+) attacks the benzene ring to from an intermediate known as - complex or a carbocation (arenium ion) which is stabilized by resonance.

The formation of intermediate arenium ion (carbocation) is slow and hence is the rate determining step of the reaction.

Benzene

+ Cl+

Chloronium ion

HCl

+

Carbocation

Slow

HCl

+ HCl

+ClH

+

HCl+

Resonance stabilized carbocation

Step 3: The carbocation loses a proton (H+) to the base FeCl-4 to give chlorobenzene.

This step is fast and hence does not affect the rate of the reaction.

+ FeCl3 + HClFast+ FeCl-4

HCl

+ Cl

Chlorobenzene

Solution : Direct addition of water to ethene in presence of an acid does not occur. Indirectly ethene is first passed through conc.H2SO4 at room temperature to from ethyl hydrogensulphate, which is decomposed by water on heating to form alcohol.

H2O

Heat

C C H OSO3H

Alkyl hydrogensulphate

C C + H2SO4

H OH

Alcohol

Mechanism of hydration of ethene to ethanol

C C + H2SO4

Alkene

Mechanism:

H2SO4 → H+ + -OSO2OH

Step 1: Protonation of alkene to form carbocation by

electrophilic attack of hydronium ion (H3O+)

H O H + H+

H H O+ H (H3O

+)

H2C+ CH3 + H2 O

Carbocation

H2C CH2 +Ethene

H H O+ H

Step 2: Nucleophilic attack by water on carbocation to yield

protonated alcohal.

Protonated alcohol

CH3 CH2

O+ H H

CH3 CH2 +

O H H

Ethyl Carbocation

+:

Step 3: Deprotonation (loss of proton) to from an alcohal.

CH3 CH2 OH + H3O+

+CH3 CH2

O H + H

O H H

:

Mechanism of Aldol Condensation (Acidity of α – Hydrogen)

The formation of aldol proceeds through the following three equilibrium steps:

Step 1: The base (OH-) on removes one of the α – hydrogen atom (which is somewhat acidic) from aldehydes and ketones to form the enolate ion which is stabilized by resonance.

The acidity of α – hydrogen is due to resonance stabilization of enolate anion.

SlowH2O + HO + H CH2 C

O

HAcetaldehyde

O

HCH2 C

:

O

HCH2 C

: :

Carbanion

Enolate ion

Step 2: The enolate ion ( strong nucleophilic) attacks the carbonyl carbon of second molecule of acetaldehydes (which acts as an electrophile ) to form the anion.

Fast O

H

CH3 C CH2 C H

O: :

Anion

O

CH3 C H +

-

+

:

O

HCH2 C

:Acetaldehyde(Electrophile)

Enolate ion(Nucleophile)

Step 3: The anion so formed takes up a proton from water to

form aldol and the OH- ion is regenerated.

O

H

O

CH3 C CH2 C H

::+ H OH

Anion

O

H

CH3 C CH2 C H

OH

+ OH-

Aldol

Aldehydes which do not contain α – hydrogen atom, such as formaldehyde (HCHO) and benzaldehyde (C6H5CHO), when treated with concentrated alkali solution undergo self oxidation and reduction, disproportionation. In this reaction one molecule is oxidised to corresponding carboxylic acid at the cost of the cost of other which is reduced to corresponding alcohol. This reaction is called Cannizzaro’s reaction.

Cannizzaro’s reaction (With concentration alkali solution)

2HCHO + NaOH → HCOONa + CH3OHFormaldehyde (50%) Sodium formate Methyl alcohol

The usual regent for bringing about the cannizzaro’s reaction is 50% aqueous or ethanolic alkali. Ketones do not give this reaction.

Benzaldehyde (50%) Sodium benzoate Benzyl alcohol2C6H5CHO + NaOH → C6H5COONa + C6H5CH2OH

Mechanism : The machanism of this reaction involve hydride ion transfer and one possibility being as follow:

Step 1. The OH- ion attack the carbonyl carbon to form hydroxy

alkoxide (Nucleophilic attack) an (I).

Fast

O

C6H5 C + OH-

H

Benzaldehyde

O-

C6H5 C OH H

Anion (I)

O C6H5 C OH

O C6H5 C O-

(Fast) -H+

Salt of benzoic acid

OH H C C6H5

H

O-

+ C6H5 C H H

(Fast) +H+

Benzyl Alcohol

Hydride transfer

(Slow)

Step 2: The anion (I) hydride ion donor to the second molecule

of aldehyde. In the final step of the reaction, the acid

and the alkoxide ion transfer H+ to acquire stability. O-

C6H5 C OH H

O + C C6H5

H

Anion (I) Benzaldehyde

Mechanism of esterification of carboxylic acid

It is a kind of nucleophilic acyl substitution. The mechanism of esterification involes the following step:

In presence of mineral acids (conc. H2SO4 or HCl gas), the carbonyl oxygen of carboxylic acid accepts a proton to form protonated carboxylic acid (I).

Step 1. Protonation of the carbonyl group.

OH

OHR C

+

+ H+

O

HR C

Carboxylic acid

OH

OHR C

+

Protonated Carboxylic acid

(I)

The electron rich oxygen atom of alcohol molecule attaches itsalf at positively charged carbon atom to form tetrahedral intermediate (II).

OH H R C O R’ OH

+

Tetrahedral imtermediate(II)

Step 2. Nucleophilic attack by the alcohol molecule

OH

OHR C

OH

R’+ :Alcohol

+

Form the resulting intermediate, a proton shifts to –OH and from another tetrahedral intermediate (III).

Proton

transfer

OH2

R C O R’ OH

(III)

+ OH H R C O R’ OH

+

Step 3: Transfer of proton.

The intermediate (III) loses a molecule of water to afford protonated ester (IV).

R C O R’ OH:

+(IV) (Protonated ester)

-H2O

Step 4. Loss of water molecule.

OH2

R C O R’ OH

+

:

(III)

The protonated ester finally loses a proton to from an ester (V).

-H+R C OR’ OH

(V) Ester

R C O R’ O H:

+(IV)

Step 5. Loss of proton.

Phenol, on refluxing with chloroform and sodium hydroxide (aq)

at 340 K followed by acid hydrolysis yield salicyladehyde

(o- hydroxy benzaldehyde) and a very small amount of p-

hydroxy benzaldehyde. However, when carbon tetrachloride is

used, saalicylic acid (predominating product) is formed. This

reaction is called Reimer – Tiemann reaction

Reimer – Tiemann reaction

OH

+ CHCl3 + NaOH(aq.)340 K

OH

CHCl2

2NaOH

-2NaCl

ONa

CHO H+

H2O

OH

CHO

2- Hydroxy benzoic acid (Salicylic acid)

Mechanism The eletrophile, dichloromethyle :CCl2 is used genrated from chloroform by the action of a base.

Reimer – Tiemann reaction involve electrophilic substitution on the highly reactive phenoxide ring.

OH- + CHCl3 HOH + :CCl3 → Cl- + :CCl2-

Chloroform Dichloro carbene(Electrophilic)

(a) C6H5OH C6H5O- + H+

Phenol Phenoxide

(b) Attack of electrophile (:CCl2) on phenoxide ion.

O-CCl2

O-

+ :CCl2

(c)O-

CCl2+ NaOH

O-CH(OH)2Hydrolysis

O-CHO

- H2O

O-CHO

+ H+

(d) OHCHO

Salicylaldehyde

T H A NKS