Nucleophilic Addition Reaction

Nucleophilic Addiation Reaction

Content...

• Introduction of NAR • Addition with Alcohols

• Addition with HCN • Addition with Grignard reagent

• Addition with NaHSO3 • Some Important Name Reaction of >C = O Group

• Addition with ammonia derivatives

Introduction of NAR
 It is characteristic reaction of carbonyl compounds.

E-Nu
C=O C – OE
|
Nu

Mechanism -


Nu E
C=O C–O C – OE
Slow (rds) | Fast |
Nu Nu

 Rate of reaction  [Carbonyl] [Nucleophile]

r = k [Carbonyl] [Nucleophile]

 attack of Nucleophile (Nu–) in rds so this type of reaction is known as Nucleophilic Addiation Reaction.

 Reactivity for Nucleophilic Addition Reaction positive Charge density on carbonyl carbon.

1

Overcrowding at carbonyl carbon

Some Important Facts :-

(i) Due to more overcrowding ketones are always less reactive then aldehydes.

(ii) Aromatic carbonyl is less reactive then aliphatic carbonyl due to -

(a) + R of phenyl group

(b) overcrowding of benzene

(iii) EWG  increase reactivity

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 Nucleophilic Addition Reaction
Examples -
(1) H C H > CH3 C H > C2H5 C H > C3H7 C H
O O O O

(2) CH3CHO < ClCH2CHO < Cl2CHCHO < Cl3C–CHO

CHO CHO CHO

(3) > >

NO2 CH3

CHO

(4) R C H >
O

(5) (a) HCHO (b) RCHO (c) Ph – CHO (d) R – CO – R (e) R – CO – Ph (f) Ph – CO – Ph

Reactivity Order of NAR - a > b > c > d > e > f

(6) (a) H – C – H (b) R – C – H (c) R – C – R (d) R – C – OR

O O O O
Reactivity Order of NAR - a > b > c > d
 Nucleophilic Addiation Reaction of carbonyl is acid catalysed.

Nu
C=O P

..  
H Nu
C=O
.. C = OH P (faster)
Fast Slow (rds)
 Nucleophilic Addition Reaction is acid catalysed when neutral Nu– are used.
 Some common Nucleophilic Addition Reaction of carbonyl group ( >C = O)

(I) Reaction with HCN -

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 Nucleophilic Addition Reaction

H2O/H R1 OH
C
R2 COOH

R1 R1 OH R1 OH
HCN Na/C2H5OH
C=O  C* C
R2 or NaCN/H R2 R2
CN CH2–NH2
Cyanohydrin
(dl-mixture)
R1 NH2
(i) NH3 C
(ii) H2O/H R2 COOH
amino acid

(II) Reaction with NaHSO3 (Sodium Bisulphite) -

OH
HOSO2Na
C=O C
OSO2Na
White crystaline solid
(Test of >C = O)

 This reaction is shown by all aldehydes but not by all ketones due to overcrowding.

 It is shown only by methyl ketones CH3COR but not CH3COPh

 BY this 2-pentanone and 3-pentanone can be differentiated.

(III)Reaction with ammonia derivatives (NH2 – Z) -

 This reaction is acid catalysed. Strong acidic medium is not suitable for catalysis.

..  
H NH3 – Z
NH2 – Z
not nucleophile

 This reaction is used for test of >C = O and separation of >C = O from a mixture.

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 Nucleophilic Addition Reaction

 (PH=4 – 4.5) Hydrolysis

C = O + H2N – Z H C=N–Z C=O
Coloured solid

 In this reaction Nucleophilic Addition Reaction followed by elimination is involved.

Mechanism -

 .. OH  OH
.. H  NH2 – Z –H elimination
C=O
.. C = OH C C C = N–Z
Fast Slow (rds) 
NH2 – Z NH – Z – H2O

Reaction of some common ammonia derivatives -

NH3
Ammonia >C = NH (Imine)

R – NH2 >C = N – R (N-alkyl imine)

1° Amine schiff base

NH2–OH
>C = N – OH (Oxime)
Hydroxyl amine


H H2N–NH2
–C– >C = N – NH2 (Hydrazone)
Hydrazine
O
carbonyl
compounds H2N–NH – Ph
>C = N – NH–Ph (Phenyl Hydrazone)
Phenyl Hydrazine

NO2
NO2
H2N–NH – –NO2
>C = N – NH– –NO2
2,4 dinitro phenyl hydrazine
(2,4 dinitro Phenyl Hydrazone)
O
O
NH2 – NH – C – NH2
>C = N – NH– C – NH2 (Semi carbazone)
semi-carbazide
 Due to high reactivity of Formaldehyde it gives urotropine with ammonia. It is used as antiseptic drug for urine

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 Nucleophilic Addition Reaction

H
C=O
NH3 Cyclic HN NH 3 H HO–CH2–N N–CH2–OH
HCHO CH2 = NH
– H2O Trimerisation
N N
H
CH2OH

– H2O NH3

N N
N

N
Urotropine

(CH2)6 N4  Molecular Formula

Hexamethylene tetra amine or hexamine
 Backmann rearrangement -
 Rearrangement of oxime into amide in presence of acid.

OH #
OH Tautomerism
R1 +
H / R1– C – NH – R2
C=N R1– C = N– R2
R2 .. O
Amide
Oxime

Example : NH2OH H+/ H2O Condensation

A B C Nylon - 6
H Polymerisation

+
H / N Tautomerism NH H 2O
Hint : N–OH Backmann H2N(CH2)5 COOH
Hydrolysis
Rearrangement aminocaproic acid
OH O
Caprolactum
– H2O Condensation

- Polyamide polymer [HN–(CH2)5 –CO ]n

- Homopolymer Nylon-6

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 Nucleophilic Addition Reaction
(IV) Reaction with Alcohols -
OR OR

ROH/H ROH/H
C=O C C
NAR NSR(–H2O)
OH OR
Hemiacetal/Hemiketal Acetal/
Ketal

SR SR SO2R

ROH/H ROH/H [O]
C=O C C C
NAR NSR(–H2O) KMNO4
OH SR SO2R
Hemiacetal/Hemiketal Thioacetal Sulphone compound
Thioketal (Sulpha drug)

OH
HOH/H
C=O C
OH
Gem. diol
(Unstable)

Example : Most easy hydration for which.

(1) CH3CHO (2) ClCH2CHO (3) Cl2CHCHO (4) Cl3C – CHO (Chloral)
Hint :Chloral forms a stable geminal diol due to -
(i) High reactivity of >C = O group.
(ii) Chelation in formed diol by IMHB

IMHB H
Cl O

H2O/H
Cl3C – CHO Cl C C Chelation

Chloral O
Cl
H
Chloral Hydrate

(V) Addition with Grignard reagent -

R R
RMgX H2O/H
C=O C C + MgX(OH)
Hydrolysis
OMgX OH
addition product 1°,2° or 3°
alcohol

(VI) Some Important Name Reaction of >C = O Group

(i) Aldol Condensation

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 Nucleophilic Addition Reaction
(ii) Canizarro Reaction
(iii) Tischenko Reaction
(iv) Haloform Reaction
(i) Aldol Condensation Reaction : Aldol reaction followed by dehydration is called aldol condensation.
Substrate  >C = O having -H
Reagent  Dilute alkali like NaOH, Ca(OH)2, Ba(OH)2 etc.
Product  Hydroxy carbonyl (aldol)

dil. alkali
Ex. CH3 – CH = O + CH3 – CH = O CH3 – CH – CH2 – CH = O
10% NaOH
OH
Hydroxy aldehyde

CH3
Ex. dil. alkali
CH3 – C – CH3 + CH2 – C – CH3 CH3 – C – CH2 – C – CH3
10% NaOH
O H O OH O
Hydroxy ketone
 During this reaction C-C bond formation between carbon of a molecule and carbonyl carbon of other molecule.
Mechanism -

H
OH– – –
CH2 – CH = O CH2 – CH = O CH2 = CH – O
– H2O
Carbanion Enolate ion
(Intermediate) (Intermediate)

CH2 – CHO HOH

CH3 – C – H CH3 – CH – CH2CHO CH3 – CH – CH2CHO
NAR – OH
O O OH
Dehydration of aldol : -
H+/
CH3 – CH – CH2 – CH = O CH3 – CH = CH – CHO + CH2 = CH – CH2 – CHO
 elimination
(Major Product) (Minor Product)
OH
unsaturated
>C = O
* Dehydration reaction can also be catalysed by base (OH–/).
Note : If product in aldol condensation reaction is directly asked -

(i) 10% NaOH 

C = O + H2 C – C – + C=C–C–
(ii) H /
O O
 Unsaturated
>C = O

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 Nucleophilic Addition Reaction
(ii) Canizarro Reaction :
Substrate - Two molecules of aldehyde without H in presence of concentrate alkali.
Product - One molecule is reduced and another is oxidised.
 Ketones can't show canizarro because ketones can't be oxidised.

Simple - Both Aldehyde moleculs same

Canizarro

Mixed - Not same molecules

 In mixed canizarro more reactive aldehyde is oxidised while less reactive is reductive.

oxidition

Conc. alkali HCOONa + CH3 – OH

2HCHO 50% NaOH (Disproportionation redox reaction)
reduction
50% NaOH
C6H 5–CHO + HCHO HCOONa + C6H 5– CH2OH (Redox reaction)
less More
reactive reactive
Mechanism - Hydride ion transfer is involved in rds

O
–
H OH H OH H–C–H Fast
C=O C HCOOH + H3C – O  H– COO + CH3OH
H H O H transfer H transfer
(rds)
Examples :
(1)

CH2 – CH3 CH2 – CH3

+
H / CH3 – C = CH – C – C2H5
CH3 – C – CH2 – C – C2H5
O
OH O O
10% NaOH
2CH3 – C – CH2 – CH3
CH2 – CH3 CH2 – CH3
+
H / CH3 – C = C – C – CH3
CH3 – C – CH – C – CH3
OH CH3 O CH3 O

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 Nucleophilic Addition Reaction
O
O
O
10% NaOH +
H /
(2)
OH

CH3 CH3
+
10% NaOH H /
(3) 2CH3 CH2 CHO CH3 – CH2 – CH – CH – CHO CH3 – CH2 – CH = C – CHO
OH

O CH3 CH3
+
10% NaOH H /
(4) 2CH3 – C – CH3 CH3 – C – CH2 – C – CH3 CH3 – C = CH – C – CH3
OH O O
(5) Ph – CHO 50% NaOH Ph – CH 2OH + Ph – COO –Na +
(6) 50% NaOH Me C – CH O + HCOO–Na+
Me3C – CHO + HCHO 3 2

CHO CHO CH2OH COO Na

– +

(7) 50% NaOH

+ +

NO2 NO2
– +
CHO COO Na
50% NaOH
(8)
CHO CH2OH

O O

10% NaOH
(9)

O OH

OH
O
H CHO
10% NaOH
(10) H

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 Nucleophilic Addition Reaction
OH CH3
O
CH3 C=O
10% NaOH
(11) H

O
Hint : In Intramolecular aldol reaction 5 or 6 membered ring formation is more important.

CH3

CH3 – CH – CH – CHO

OH
Cross product

CH3 – CH2 – CH – CH2 –CHO

10% NaOH
(12) CH3 – CHO + CH3 – CH2 – CHO OH

CH3 – CH – CH2 – CHO

OH
Self product
CH3

CH3 – CH2 – CH – CH – CHO

OH

Simple Aldol reaction

Note : Aldol reaction

Mixed Aldol reaction

 In mixed aldol reaction for major product.
Case - I - If both are aldehyde then consider more reactive hydrogen.
Case - II - If atleast one ketone is present then consider more reactive carbonyl group.

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 Nucleophilic Addition Reaction

CH3 – CH – CH2 – CHO

OH

Self product
CH3
O CH3 – C – CH2 – C – CH3
(13) CH3 – CHO + CH3 – C – CH3 10% NaOH OH O

CH3 – CH – CH2 – C – CH3

OH O
(Major)
Cross product

CH3

CH3 – C – CH2 – CHO

OH

Ph – CH – CH2 – CHO Cross product

OH
(Major)
10% NaOH
(14) CH3 – CHO + Ph – CHO

CH3 – CH – CH2 – CHO Self product

OH

CH3 – CH – CH2 – NO2 Cross product

OH
(Major)
(15) CH3 – CHO + CH3– NO2 10% NaOH

CH3 – CH – CH2 – CHO Self product

OH

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 Nucleophilic Addition Reaction
– + – +
COOH 50% NaOH COO Na COO Na
(16) +
– +
CHO CHO COO Na

50% NaOH +
(17)
CHO O
CH2OH COO–Na+
O O

50% NaOH
Ph – C – CHO Ph – CH – COO Na
– +

(18)
O OH

(19)

CH3 CH3 CH3 CH3

– H2O CH3COCH3
CH3 – CH – CH2 – CH – CH3 CH3 – CH = CH – C – CH3 CH3 – C = C – C = C – C– CH3
– H2O
OH O O O

CH3
CH3 – C = C – C = CH = C
CH3
CH3

(20)

50% NaOH/  –H2O

CH3 –CHO–CHO CH3 – C – CH2 – CHO CH3 – C = CH – CHO CH 3 –C=CH–CH–CHO
CH3CHO
OH repeatition

Polymer - Brewn resin

Test of aldehyde

10% NaOH
H – C – CH2 – CHO
aldol reaction
OH
(21) CH3CHO + HCHO

50% NaOH
Repeating aldol
C(CH2OH)4 + HCOONa
then canizaro Penta erythrotal

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 Nucleophilic Addition Reaction

H
C=O
(22) CH CHO + HCHO aldol reaction H (HOCH2)2 CHCHO
3 CH2 – CH2 CHO aldol reaction

OH aldol H
reaction C=O
H

HCHO
C(CH2OH)4 + HCOONa (HOCH2)3 CHO
Mixed Canizarro

(iii) Modified Canizarro (Tischenko Reaction) -

Substrate - Aldehyde (H may presence or absence)
Reagent - Aluminium ethoxide
Product - Firstly alcohol and acid are obtained with converts into ester.

Al(OC2H5)3 ..
2HCHO [CH3 – OH + HCOOH] esterification CH3 – O – C – H
O
Methyl formate

Al(OC2H5)3 –H2O
Examples : 2CH3CHO CH3 CH2OH + CH3COOH
esterification CH3 – C – OCH2CH3
O
ethyl acetate
(iv) Haloform Reaction - Formation of Halform involved in this reaction.
 Iodoform is yellow crystaline solid so Iodoform formation is also called Iodoform test.
Substrate  - mathyl > C = O
Reagent X2 + base
Product CHX3 (Haloform)
X2 + Base
CH 3– C – R CHX3 + R – C – O
O O
 By OX 1° and 2° alcohol (not 3° alcohol) may be oxised into carbonyl compounds.
 1° and 2° alcohols with give methyl >C = O on oxidation are also suitable in Holoform reaction.
Mechanism -

H O O
OH Cl Cl
CH2– C – R CH2 = C – R Cl – CH2 – C – R Cl3C – C – R
–H2O
( Halogination)
O O
 By excess base it is hydrolysed to give haloform.

O O

OH H transfer
Cl3C – C – R R – C – OH + CCl3 R–C – O + CHCl3
NSR
O
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 Nucleophilic Addition Reaction
Examples : Give product in following reaction.
O
(1) Cl2 + NaOH
CH3 – C – H CHCl3 + HCOO– Na+
O
Cl2 + Ca(OH)2
(2) CH3 – C – CH3 CHCl3 + (CH3– C – O)2 Ca
O

OBr (aq.)
CH3 – CH – CH3– CH3 CHBr3 +CH3 – CH2 – C– O
(3) Br2 +OH
O O
CaOCl2 (aq.)
(4) CH3 – C – CH3 CHCl3 + (CH3 – C – O)2Ca
Bleaching
O Powder O

Cl2/NaOH Cl2/NaOH
(5) CH3–CH2 – OH CH3–CHO CHCl3+ HCOONa
Oxidation
Br2/NaOH Br2/NaOH CHBr + CH – CH – COONa
CH3–CH– CH2 – CH3 CH3– C – CH2 – CH3 3 3 2
(6) Oxidation
OH O
Br2/NaOH Br2/NaOH Br2/NaOH
CH3–CH–CH3 CH3–CH –CH3 CH3– C – CH3 CHBr3 + CH3 – COONa
(7) Oxidation
Cl OH O
Cl OH
Cl2/NaOH –H2O Cl2/NaOH
CH3–C –CH3 CH3–CH –CH3 CH3– C – CH3 CHBr3 + CH3 – COONa
(8)
Cl OH O
Cl2 + NaOH
(9) CH3 – C – Cl no reaction
O
Hint : Acid and acid derivatives are not suitable for haloform reaction because Hydragen is not so reactive due to
cross conjugation.
 ..
CH3 – C – Z –H
CH2 – C – Z
O O
(No tautomerism)
Haloform
reaction CHCl3 + HCOONa
(Main reaction)
50% NaOH
(10) Cl3C – CHO
Chloral
Canizaro
reaction Cl3C – CH2OH + Cl3C – COONa
(side reaction)

Hint : CCl3 is good leaving group so haloform reaction is more favourable then canizarro in chloral.

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 Nucleophilic Addition Reaction
(V) Borodine Hunsdicker Reaction -
Br2
R – Br+CO2 + AgBr
CCl4

R – C – OAg
O Cl2
R – Cl + CO2 + AgCl
CCl4
Mechanism -
Br2
R – C – OAg R – C – O – Br + AgBr
O O
 . .
R – C – O – Br R – C – O + Br
O O

. .
R–C–O R + CO 2
O

. .
R + Br RBr
(Major product)

. .
R+R–C–O R – C – OR
O O
(Ester)

*
.
If I2 Taken  major product ester due to Bulky I , this reaction is known as birn baum simoni reaction.
Quanitity of product - 1° > 2° > 3° halide
R – Cl > R – Br > R – I

CH2 – COOH AgOH Br2/CCl4 KCN Complete 

Qus. A B C D E
CH2 – COOH Hydrolysis

CH2 – COOH AgOH CH2 – COOAg Br2 CH2 – Br KCN CH2 – CN Complete CH2 – COOH
Sol.
CH2 – COOH CH2 – COOAg CCl4 CH2 – Br CH2 – CN Hydrolysis CH2 – COOH
(A) (B) (C) (D) 

O
CH2 – C
O
CH2 – C
O
(E)

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 Nucleophilic Addition Reaction
(VI) Perkin Condensation -

Substrate - H containing aliphatic Anhydride + Aromatic aldehyde

Reagent - R-COONa/Hydrolysis/

Product -  unsaturated carboxylic acid

O O
Ph R–COONa Ph
C = O + H2 C – C – O – C – CH3 Hydrolysis C = CH – COOH
Ex. H H
H

Mechanism -

O Ph–C – H
R – C – O¯ O
CH2– C– O –C–CH3 CH2– C– O –C–CH3 Ph– CH– CH2 –C – O –C –CH3
–R – COOH
H O O O O O O O

RCOOH

 H2O
Ph – CH = CH – COOH Ph– CH– CH2 –C – OH Ph– CH– CH2 –C – O –C –CH3
–H2O
 unsaturated OH O OH O O
carboxylic acid

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