1. REACTION INTERMEDIATES
&
MECHANISM
Presented By
Jasmeen Quadir
KV No. 3
Bhopal

2. Reaction Intermediates
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.

3. 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

4. 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:
Inductive Effect
Resonance Effect
Hyperconjugation Effect

5. 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 30 H 20 10
Methyl carbocation
>
Stability decreases as +I-effect of the alkyl group decreases
(CH3)C > CH3CHCH3 > CH3CH2CH2 > CH3CH2 > CH3 +

6. (b) Resonance effect
Carbocations in which the +vely chared carbon atom is attached to a double bond or a benzene ring are stabilized by resonance.
CH2 CH ─ CH ↔ CH2 ─ CH CH2
(Allyl carbocations is stabilized by resonance) +
More the number of phenyl group, greater is the stability.
(C6H5)3C+ > (C6H5)2CH+ > C6H5CH2+

7. Hyperconjugation effect
Tert – 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

8. The stability of the various carbocations decreases in the order:
(C6H5)3C+ > (C6H5)2CH+ > (CH3)3C+ > C6H5CH >
(CH3)2CH+ > CH2 = CH ─ CH > RC = CH2 > CH3CH2+ >
RCH = CH+ > C6H > CH > HC ≡ C+ +

9. Reactivity
The 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°>

10. Orbital structure of carbocations
The 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°.
EMPTY p-ORBITAL R  C+
1200 R  
sp2 – HYBRIDIZED CARBON R
Orbital structure of carbocations

11. 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 ─ CHO
Hydroxide ion
Acetaldehyde ion
Acetaldehyde carbocation - :
H2N H─ C≡C ─ H → NH C≡C─H
Amide ion
Acetylene

12. > Stability Inductive effect
The stability of simple alkyl carbanions follow the order: CH3- > 1°> 2°> 3°.
>
C:- H
Methyl carbonion R 10 20 30

13. -: (b) Resonance effect - -
Allyl and benzyl carbanions are stabilized by resonance.
CH CH ─ CH ↔ -CH2 ─ CH CH2
(Allyl carbanion is stabilized by resonance) -
:CH2 -
CH2 :- : -:
(Benzyl carbanion is stabilized by resonance)
(C6H5)3C- > (C6H5)2CH > C6H5CH-2

14. s- Character
Stability 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- character
33% s- character

15. Reactivity Orbital structure
The order of reactivity of carbanions is reverse of the order of stability, 30 > 20 > 10 > CH-3
Orbital structure
The 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.

16. Orbital structure of carbanions
sp3 - ORBITAL
LONE PAIR
. .
sp3 – HYBRIDIZED
CARBON C- R  R  R 
Orbital structure of carbanions

17. Free Radical Classification
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 cleavage
Chlorine free radicals
Chlorine
Classification R 
R ─ CH2
Secondary (20) R 
R ─ C ─ R
Tertiary (30)
R ─ CH2
Primary (10)

18. 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 ─ CH
Isopropyl free radical
(20)
CH3 ─ CH2
Ethyl free radical
(10)
Methyl free radical
>
The stability of the various free radicals in the order.
(C6H5)3C > ( C6H5)2CH > C6H5CH2 >
CH2=CH─CH2 > (CH3)3C > (CH3)2CH >
CH3CH > CH > CH2=CH > HC≡C

19. Orbital structure of free radicals
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.
p-ORBITAL .
UNPAIRED ELECTRON R 
1200 C R  R 
sp2 – HYBRIDIZED CARBON
Orbital structure of free radicals

20. Mechanisms of nucleophilic substitution reaction
There are two type of nucleophilic substitution reaction:
SN1 Mechanism (unimolecular nucleophilic substitution)
SN2 Mechanism (Bimolecular nucleophilic substitution)

21. SN1 Mechanism (unimolecular 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]
THIS TYPE OF REACTION PROCRRDS IN TWO STEP AS:

22. 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.
R ―X R X-
Slow step
Carbocation
CH3 
CH3  C  X
Tert. butyl halide
CH3 
CH3  C+  X-
Carbocation
Slow step

23. 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.
R +― :Nu R ― Nu
Fast step
CH3 
CH3  C OH-
Tert. butyl carbocation
Nucleophile
CH3 
CH3  C  OH
Tert. butyl alcohol

24. R3C ― X > R2CH ― X > R ― CH2 ― X > CH3 ― X
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 SN1 reaction is favored by heavy (bulky) group on the carbon atom attached to halogens.
R3C ― X > R2CH ― X > R ― CH2 ― X > CH3 ― X
Tertiary
(30)
Secondary
(20)
Primary
(10)
and nature of carbocation in substrate is:
SN1 Order:
Benzyl > allyl > 30 > 20 > 10 > methyl halides

25. Rate  [Substrate] [Nucleophile]
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 SN2 , the second order change
Rate  [Substrate] [Nucleophile] or
Rate = k [ RX ] [ :Nu- ]

26. Hydrolysis of methyl chloride is an example of SN2 reaction and high reaction concentration of the nucleophile (OH-) favours SN2 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  -

27. 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.
  -
HO C Cl  H
H O C  Cl  H
Transition state H 
HO  C  H + Cl-
Alcohol

28. 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 + -
C  Br
H3C
n – C6H13
(–) -2 - Bromooctane H
H O  C
CH3
n – C6H13
(+) Octan – 2 – ol
H Br-

29. SN2 order : CH3  X > RCH2  X > R2CH  X > R3C  X
Primary
Secondary
Tertiary
The nature of carbocation in substrate is :
SN2 order :
Methyl > > > > allyl > benzyl halides

30. MECHANISM OF HALOGENATION
Halogenation of benzene is an electrophilic subsititution reaction.

31. Step 1. The electrophilic, i,e
Step 1. The electrophilic, i,e., halonium ion (Cl+, Br+ or I+) is generated by the action of Lewis acid (FeCl3 or anhyd. AlCl etc.) on the halogens.
Cl ― Cl + FeCl3 → Cl Fecl-4
(Electrophile)

32. + Cl+ + + + H Cl + H Cl H Cl Cl H
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. H Cl +
Carbocation
Benzene
+ Cl+
Chloronium ion
Slow H Cl + H Cl + Cl H +
Resonance stabilized carbocation
The formation of intermediate arenium ion (carbocation) is slow and hence is the rate determining step of the reaction.

33. + + FeCl-4 H Cl Cl + FeCl3 + HCl
Step 3: The carbocation loses a proton (H+) to the base FeCl-4 to give chlorobenzene.
+ FeCl-4 H Cl + Cl
Chlorobenzene
Fast
+ FeCl3 + HCl
This step is fast and hence does not affect the rate of the reaction.

34. Mechanism of hydration of ethene to ethanol
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.
 
C  C  + H2SO4
H OH
Alcohol
 
 C  C 
H OSO3H
Alkyl hydrogensulphate
 
 C C  + H2SO4
Alkene
H2O
Heat

35. Mechanism:
H2SO4 → H OSO2OH

36.     Step 1: Protonation of alkene to form carbocation by
electrophilic attack of hydronium ion (H3O+) H 
H  O+  H (H3O+) 
H  O  H + H+  H 
H  O+  H 
H2C CH2 +
Ethene
H2C+  CH3 + H2 O 
Carbocation

37.   : Step 2: Nucleophilic attack by water on carbocation to yield
protonated alcohal.
CH3  CH2 +
O  H  H 
Ethyl Carbocation + :
Protonated alcohol
CH3  CH2 
O+  H  H 

38.  : Step 3: Deprotonation (loss of proton) to from an alcohal.+
CH3  CH2 
O  H +  H 
O H :
CH3  CH2  OH + H3O+

39. (Acidity of α – Hydrogen)
Mechanism of
Aldol Condensation
(Acidity of α – Hydrogen)
The formation of aldol proceeds through the following three equilibrium steps:

40. 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.
HO + H  CH2  C  O H
Acetaldehyde O H
CH2  C :
CH C 
Carbanion
Enolate ion
Slow
H2O +
The acidity of α – hydrogen is due to resonance stabilization of enolate anion.

41. 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. O
CH3  C H + - + :  H
CH2 C
Acetaldehyde
(Electrophile)
Enolate ion
(Nucleophile) O H 
CH3  C  CH2 C  :
Anion
Fast

42. Step 3: The anion so formed takes up a proton from water to form aldol and the OH- ion is regenerated. O H
CH3  C  CH2  C  : 
+ H  OH
Anion O H 
CH3  C  CH2 C OH
+ OH-
Aldol

43. Cannizzaro’s reaction (With concentration alkali solution)
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.

44. 2HCHO + NaOH → HCOONa + CH3OH
Formaldehyde
(50%)
Sodium formate
Methyl alcohol
Benzaldehyde
(50%)
Sodium benzoate
Benzyl alcohol
2C6H5CHO + NaOH → C6H5COONa + C6H5CH2OH
The usual regent for bringing about the cannizzaro’s reaction is 50% aqueous or ethanolic alkali. Ketones do not give this reaction.
Mechanism : The machanism of this reaction involve hydride ion transfer and one possibility being as follow:

45. Step 1. The OH- ion attack the carbonyl carbon to form hydroxy
alkoxide (Nucleophilic attack) an (I). O
C6H5  C + OH-  H
Benzaldehyde O- 
C6H5  C  OH H
Anion (I)
Fast

46. 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
Anion (I)
Benzaldehyde O
C6H5  C OH
C6H5  C  O-
(Fast) -H+
Salt of benzoic acid OH 
H C  C6H5 H O-
+ C6H5  C  H
(Fast) +H+
Benzyl Alcohol
Hydride transfer
(Slow)

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

48. Protonated Carboxylic acid
Step 1. Protonation of the carbonyl group.
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). OH
R  C  +
Protonated Carboxylic acid
(I)
+ H+ O H
R  C 
Carboxylic acid OH
R  C  +

49. Tetrahedral imtermediate
Step 2. Nucleophilic attack by the alcohol molecule
The electron rich oxygen atom of alcohol molecule attaches itsalf at positively charged carbon atom to form tetrahedral intermediate (II). OH
R  C  O H 
 R’ + :
Alcohol
OH H
 
R  C  O  R’  OH  +
Tetrahedral imtermediate
(II)

50. Step 3: Transfer of proton.
Form the resulting intermediate, a proton shifts to –OH and from another tetrahedral intermediate (III).
OH H
 
R  C  O  R’  OH +
OH2 
R  C  O  R’ OH
(III) +
Proton
transfer

51.  : : Step 4. Loss of water molecule.
The intermediate (III) loses a molecule of water to afford protonated ester (IV).
OH2 
R  C  O  R’ OH + : 
(III)
-H2O
R  C  O  R’ OH : +
(IV) (Protonated ester)

52. Step 5. Loss of proton.
The protonated ester finally loses a proton to from an ester (V).
-H+
R  C  O  R’
O  H : +
(IV)
R  C  OR’ OH
(V) Ester

53. Reimer – Tiemann reaction
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

54. OH OH CHCl2 + CHCl3 + NaOH(aq.) ONa CHO OH CHO 340 K  2NaOH H+ -2NaCl
2- Hydroxy benzoic acid
(Salicylic acid)
2NaOH
-2NaCl H+
H2O

55. Mechanism
The eletrophile, dichloromethyle :CCl2 is used genrated from chloroform by the action of a base.
OH- + CHCl HOH + :CCl3 → Cl- + :CCl2 -
Chloroform
Dichloro carbene
(Electrophilic)
Reimer – Tiemann reaction involve electrophilic substitution on the highly reactive phenoxide ring.

56. (b) Attack of electrophile (:CCl2) on phenoxide ion.
(a) C6H5OH C6H5O H+
Phenol
Phenoxide
(b) Attack of electrophile (:CCl2) on phenoxide ion. O-
+ :CCl2 O-
CCl2

57. O- CCl2 + NaOH O- CH(OH)2 (c) O- CHO (d) O- CHO + H+ OH CHO Hydrolysis
Salicylaldehyde

58. T H A N K S