Named Reactions 186

CHAPTER

6
Named Reactions
6.1. Aldol Condensation
Aldehyde containing an -hydrogen atom undergoes a reversible self addition in presence of the dil. acid or
usually in alkali to give condensation product -hydroxy aldehyde or ketone. In every case the addition occurs
in such a way that -carbon of the first carbonyl compound get attached to the carbonyl carbon of the second.
OH
OH–/H+
CH3 CHO + CH3CHO CH3 CH CH2 CHO
-hydroxy aldehyde
CH3
OH–/H +
CH3COCH3 + CH3COCH3 CH3–C–CH2–CO–CH3
OH
-hydroxy ketone
Note: If an aldehyde and ketone do not contain -H, the self condensation reaction donot occur.
e.g. ArCHO, HCHO, (CH3)3C-CHO, Ar-CO-Ar,
Ar–C–CR3 can’t undergo self condensation due to absence of  H-atom.
O
Mechanism:
(1) Base - Catalysed mechanism
(a) Addition Phase : Nucleophilic addition.
O O
R CH2 C R ' + B R CH C R ' R CH C R '
enolate ion
O
O R' O
R CH2 C R ' + R CH C R' R CH2 C CH C R '
(E+ partner) O (Nu– partner) O R
R' O
BH
R CH2 C CH C R '
Proton transfer
OH R
Aldol

Proton transfer reactions are always reversible reaction.

Named Reactions 187
(b) Dehydration Phase :
R' O R' R' O
B– E1CB
R CH2 C CH C R' R CH2 C C COR + BH R CH2 C C C R
Mech.
OH R OH R R
-unsaturated aldehyde / ketone

In general the aldol reaction is reversible in both acidic and basic condition, but when reaction conditions are
favourable to cause dehydration, predominantly in acidic medium the reaction goes to completion.
The reaction is unfavourable usually for acyclic ketones this is because -
1. Carbonyl carbon of the ketone is less electrophilic because of the +I effect of the alkyl groups.
2. Due to steric hindrance the probability of nucleophilic attack by enolate or enol is decreased.
(2) Acid Catalysed Mechanism :
Enol is less nucleophilic than enolate.
(a) Addition Phase :
O O H OH
(i) R CH2 C R ' + HA R CH2 C R' + A –
R CH C R'
Enol

R' O
–H
(ii) R CH2 C R ' + R CH C R ' R CH2 C CH C R '
O H O H OH R
Protonated E+ Aldol
(Better electrophile than the
unprotonated aldehyde/ketone)

(b) Dehydration Phase :

R' O R' O
H+
R CH2 C CH C R' R CH2 C CH C R'
Proton transfer
OH R OH2
R

R' H O R' O
– H2O – H+
R CH2 C C C R' R CH2 C C C R'
Better L.G.
E1 Mechanism R R
Experimental Evidence :
Aldehyde :

O O O
(1) OH–
CH3CHO CH2 C H CH2 C H + H3C C H
(2)

H2O
CH3 CH CH2 CHO CH3 CH CH2 CHO

OH 45% O
Named Reactions 188
Ketone :

O O O
(1) OH–
H3C CO CH3 H2C C CH3 H2C C CH3 + C CH3

(2) H3C

CH3 CH3
H2O
H3C C CH2 C CH3 H3C C CH2 C CH3
OH O O O

Carrying out a reaction with D2O fails to result in the incorporation of any deuterium to the CH3 group of
aldehyde to produce D CH2 CHO but it produces D–CH2–COCH3 in case of ketone. This indicates that
the step two is faster than reversal of state one in case of aldehyde and slower in case of ketone.
The reaction can be made of synthetic importance by :
(1) Continuous distillation of the products in a Soxhlet Apparatus (Reaction move forward following Le -
Chatelier Principle) using Ba(OH)2 base.
(2) Using acid catalysis tendency of dehydration of aldol products is increased producing more stable -
unsaturated aldehyde / ketone
(3) To stop at the aldol stage the best catalyst are basic ion exchange resin.
(4) A 3o alcohol always undergoes dehydration through E1 mechanism. E1  3o  2 o  1o 

Me O O
H+ CH3COCH3
Me C CH COMe Me2C=CH–C–Me Me2C CH C CH CMe2
– H2O Mesityl oxide HCl
Phorone
OH H
Example:
O OH
O
OH C CH C
(i)
O CH3

O O
O O
O
(iii) O Dowex-50 O
(ii) H+
H+

(iv) NaOEt
C7H15CHO C7H15 CH C CHO
C6H13
O O

Ba(OH)2
(v)
Named Reactions 189

Crossed-Aldol / Mixed Aldol : (Claisen-Schmidt Condensation)

When one of the partner in a crossed aldol condensation is benzaldehyde which can only act as a E+ and any
other aldehyde or ketone which can form either enol or enolate then this type of mixed condensation is known
as Claisen - Schmidt Condensation.
O
H
C H C CH CHO
CH3CHO
KOH Cinnamaldehyde

H
CH3 CO CH3
C CH C CH3
HCl O
H
C CH C Ph
CH3COPh
O
Electron donating groups in benzaldehyde will make the reaction slower and e– withdrawing groups make the
reaction faster.

O
O OH
NaOH CH3NO2 NO2 H2O NO2
NaOH
Henry
Aldol condensation Nitro alcohol

Conditions For Crossed Aldol :

(i) Only one enolizable component (aldehyde / ketone having -H)
(ii) No other compound containing more acidic hydrogens than aldehyde/ketone eg. CH3NO2
(iii) The carbonyl E+ should be more reactive than the compound being enolised)
Example:
O

1. C CH2 O O O O OH
KOH
+ Ph C H C CH2 CH Ph C CH2 CH Ph
MeOH
–H2O (E1cb)
O
C C CH Ph
H
CH3
O O CH3 CH3
O OH
OO
2. H NaOMe MeOH
CH CH
O O O
H2O
CH3
O

CH
O
Named Reactions 190

O O OH
CH3 CH3
C H O
CH CH CH CH
+ CH3 CH C Et COEt EtOH COEt
3. CH2OH
CH2OH CH2OH
(E1 cb) H2O
H CH3
C C
COEt
CH2OH
Retro Aldol : Because the aldol reaction is reversible, so when the aldol product is heated with a strong base
then it reverse back to an equilibrium mixture which mainly contain initial reactant.

OH O O O O
OH
CH3 C CH2 C CH3 CH3 C CH2 C CH3 CH3 C CH3 + H2C COCH3
CH3 CH3 H2O
5% in equilibrium mixture
2 CH3COCH3
95% in equilibrium
mixture
PROBLEMS

O
(i) LDA- 78oC , THF
?
1. Ph O
(ii)

O OLi
LDA
Ph Ph
Soln. H Li N

O Li O O O
O H2O OH
+
Ph Ph Ph

Aldol
O
(i) LDA
2. (H3C)2HC CH(CH3)2
?
O
(ii)
H
O O O
O
+
(H3C)2HC C(CH3)2 H (H3C)2HC C CH
H3 C CH3
O Li
Soln. O OH
(H3C)H2C C(CH3)2
(H3C)2HC
H3 C CH3
Named Reactions 191
6.2. Baeyer - Villiger Oxidation Reaction
Oxidation of ketone to ester by reacting reactant (ketone) with hydrogen peroxide or peroxy compound or
peracid( RCO3H) in presence of acid catalyst.
O O
O +
H
R C R' + R'' COOH R COR' + R''CO2H
Mechanism :

OH OH OH O
O
H+ R''CO3H R" COO – H+
R C R' R C R' R C OR R C OR
R C R'
O
O
OH
C O
R C R'
R"
When unsymmetrical ketones are used, then order of migration of alkyl group, is : tert-alkyl, sec-alkyl >
Benzyl, Phenyl > Prim - alkyl > cyclopropyl > methyl. For Benzophenone, p-OCH3 > CH3 > H > Cl >
NO2 in para - position.
Note: Peroxy trifluoro acetic acid and m-chloro peroxy Benzoic acid can also be used :
Examples:
O O
CH3COOOH
(i) O2N C H O2N C O H
HOAc, H2SO4

O O O O
RCO3H
(ii) CH3 C C CH3 CH3 C O C CH3

O
O
CH3
m-CPBA O
(iii)
CH3 CH2Cl2 CH3
CH3

C4H9 C4H9
m-CPBA
(iv)
H2SO4 O
O
O

CH3COOOH
(v) O O
H+
O

O O

O
(vi) CF3 COOOH
H+

O
(vii) CF3CO3H O
H+ O
Named Reactions 192

O
(viii) CF3COOOH
C O O C CH3
H3C H+

Cl
Cl
CF3COOOH
(ix) C CH3 O C CH3
Cl H+
Cl
O O

PROBLEMS
•
O HO• R
O O O R
R CF3CO3H O C C
(i)
CF3 O
by migration of Ph

BnO BnO

(ii) m-CPBA
O O
O

O O
(iii) Ph Ph O Me Ph
Me OMe
+
Me Me O Me
(Major) (Minor)

O
O
(iv) HOAc
O

O
O
OAc O
(v) m-CPBA, CF3SO3H
OAc
CH2Cl2, 45 min, 90%

6.3. Benzoin Condensation

Condensation of aromatic aldehyde in presence of CN– ion to give condensation products called benzoin, is
known as Benzoin Condensation.
O
CN
2 Ar CHO Ar CH C Ar
OH
2
When Ar = Ph, it is called benzoin rate law r  K  ArCHO   CN  
Named Reactions 193
The reaction involves attack of CN– ion on the carbonyl carbon but in this reaction instead of H– transfer (as
that of cannizzaro reaction) it is now a carbanion addition of the one aromatic aldehyde to the carbonyl carbon
of the other aromatic aldehyde. The reaction is of 3rd order.

O O OH
Step - 1
OH
Step - 2
Ph C H Ph C H Ph C
CN Ph C
intramolecular
CN H-abstraction C N C N

OH O OH O O HO
Step - 3
O HO
Ph C H CN
Ph C Ph C C Ph Ph C C Ph Ph C CH Ph
C N Benzoin
CN H CN H -hydroxy ketone

1. This reaction is completely reversible, the reversibility indicated by the fact that when benzoin is heated with an
another aromatic aldehyde, mixed products are obtained.
H KCN
Ph C C Ph + 2Ar' CHO 2 Ph CH C Ar'
HO O HO O
This reaction is intermolecular mixed product
reversible reaction
2. CN– catalyses the reaction because :
(i) It is good nucleophile
(ii) It is good leaving group
(iii) It increases the acidity of the C–H bond and stabilises the carbanion that results from the loss of proton
from C.
3. Benzoin is a colourless solid (M.P. 157oC) which assumed to tautomerise to ene diols.

H O OH OH
C C C C
OH Ene diole

Reduction of Benzoin :
2[H] * *
Ph CH CH Ph Hydrobenzoin
Na/EtOH
OH HO (Pinacol)

2[H]
Ph CH2 C Ph Deoxybenzoin
Sn/HCl
O
Ph CH C Ph
H
OH O [H] KOH/EtOH
Ph CH CH Ph Ph CH CH Ph
Zn/Hg, HCl E2
Stilbene
OH

4 H2
Ph CH2 CH2 Ph Dibenzyl
Ni/H2
Named Reactions 194
Oxidation of Benzoin :
CHO COOH
CrO3
+

[O]
Ph CH C Ph Ph C C Ph Benzil
HNO3
OH O O O
[O]
Ph C C Ph
CuSO4, Py
O O
6.4. Birch Reduction
Reduction of aromatic ring by means of alkali metals (sodium or lithium) in liquid ammonia or amine with
ethanol as proton donor to give mainly conjugated dihydro derivatives. Ethers are sometimes used as a co-
solvent to dissolve the aromatic compound. Use of t-butanol fulfils the dual role of proton donor and co
solvent.
R R R
Na, NH3(liq)
or where
alcohol E.W  electron withdrawing group.
E.R.  electron releasing group.
where R R is E.W.Group
is E.R.Group
Mechanism : Solvated electrons are reducing agent.
Na (NH3) Na+ (NH3)X + e (NH3)X
R R R R
R H
e– ROH –
e ROH

H H H H H H H
Radical anion Radical anion Product
Effect of Substituent on Aromatic Ring (Regioselectivity) :
Electronic Factor : Electron withdrawing groups make the ring more susceptible towards reduction and
hence increases the rate of reaction on the other hand electron donating groups decrease the rate of reaction.
Electron withdrawing groups promote ipso & para reduction whearas electron donating groups promote meta
and ortho reduction.

Ipso
OCH3 OCH3
COOH COO Li COOH
H Li, NH3(l) H
(i) Li, NH3(l) H+ (ii)
EtOH H
EtOH H
+
E H H para H
HOOC LiOOC o,m-reduction
E E Ipso, para-reduction
H+
Named Reactions 195
To Produce Cyclohexanones :
H
OCH3 O O O
+ H
H3O
H+
– CH3OH

Example:

Li/Et2NH
+
(i) MeNH
80% 20%

CH2OH Li, NH3 (COOH)2 CH2OH

(ii) H2O, t-BuOH
MeO O

OMe OMe

(iii) Li, NH3

N N
t-BuOH

1) Li, NH3 , EtOH HOOC

(iv) COOH
2) Br
H H

H H
1) Li, NH3 OCH3 OCH3
OCH3 H+
(v) +
2) H , H2O H3C
H3C
H3C
H H
OMe
O O OMe
1) K, NH3 , t – BuOH Et
(vi) N
N
2) Et–I
OMe OMe

6.5. Cannizzaro Reaction

Under the influence of strong and conc. base, aldehyde which has no -H (non enolazable) undergoes self
oxidation reduction reaction (disproportionation) to produce corresponding alcohol and acid. This is knwon as
Cannizzaro reaction.

e.g. Aldehyde - HCHO, PhCHO, R3C– CHO, CHO

O
Named Reactions 196
Aldehydes which have -H undergo aldol reaction much faster than the cannizzaro reaction.
1) Conc.NaOH
2 PhCHO Ph COOH + PhCH2OH
2) H3O+
Benzoic acid Benzyl alcohol
(Oxidised) (Reduced)

Disproportionation
Mechanism: The mechanism involves intermolecular hydride transfer
OH O OH O
OH RDS Ph
Ph C H Ph C H + C Ph Ph C + C
fast Slow H
O H O H
O
Nu– donar E+ acceptor
H3O+
PhCOOH + PhCH2OH Ph C O + PhCH2OH
acidic work up
O
Rate = K[PhCHO]2[OH–] 3rd order reaction
Cannizzaro reaction is a third order reaction.

6.6. Clemmensen Reduction:

Ketone and aldehyde on reduction with zinc amalgam and hydrochloric acid give the corresponding hydrocarbon
i.e, carbonyl group is converted into methylene group.
O H2
Zn/Hg C
C
R HCl R
R' R'
The mechanism of Clemmensen reduction is uncertain. The following expected reaction pathway involve the
transfer of electron from the metal surface to the carbon atom of the protonated carbonyl group. Transfer of
4e– from Zn to one molecule is expected to occur.
Mechanism :

O OH OH
H+ Zn, Cl H+
C C – R C R' R C R'
e transfer
R R' R R' – H2O
ZnCl ZnCl
2Zn
H H+ R' + 2Zn+
H+ R C R' R C
ZnCl2 + R CH2 R'
ZnCl ZnCl
Special Features:
(i) The acid should be conc. (aq. phase should be low) to prevent the bimolecular condensation reaction
of carbonyl compound.
(ii) The reduction fail with acid sensitive and high molecular weight substrate.
(iii) Certain types of aldehyde and ketones do not give the normal reduction products alone.
C.R.
(a) CH3 C CH2 C CH3 CH3 C CH CH3
O O O CH3
Named Reactions 197
Mechanism :
Through Rearrangement
Zn
H+ H+ O
O O OH2
HO OH HO OH HO OH
H
CH3
[H] – H2 O
H3C C CH
O CH3 O
O CH3

O
O
O O NH2NH2/KOH O O H3 O+ Zn-Hg
(b)
ethylene HCl
glycol

This ring is stable

in basic medium. In acidic medium
it will be broken.

Application :
(1) To reduce keto acid :
O CH2 CH2 CH2COOH
Zn-Hg
C CH2CH2COOH
HCl

(2) To prepare naphthalene :

O
C
CH2 1) Zn-Hg, HCl AlCl3 Zn-Hg Se
CH2 2) SOCl2 HCl 
COOH O
Cl O
Example:
C.R.
(i) Ph C C3H7 Ph CH2 C3H7
O
(ii) CH3(CH2)7 C.R.
CHO CH3(CH2)7 CH3

Cl 1) AlCl3 2) Zn-Hg
Se
(iii) HCl 
O
O
O
C.R.
(iv) Ph Ph
14 14

OH
OH
OCH3 OH O OH
Zn/Hg OCH3
C(CH2)5CH3 CH2 (CH2)5CH3
(v) HCl (vi) HCl
Zn(Hg)
CH O CH3 (81– 86)%
(60 – 67)%
Named Reactions 198

O O
Zn(Hg)
(vii) C C CH2 CH2
HCl
CH3 CH3
Zn(Hg)
(viii) HCl
O
H H
6.7. Cope eliminations:
(Thermally syn elimination of N-oxide to less substituted Olefins as major)
The formation of an Olifin and a hydroxylamine by thermal decomposition of tertiary amine oxide is known as
cope elimination. The N-oxide derivatives are prepared by the oxidation of corresponding tertiary aliphatic or
aromatic amines with aqueous hydrogen peroxide or m-chloroperbenzoic acid.

O
R3
H R OH
N 
+ N
R R2
R1 R2 R3 R1
The reaction takes place at much lower temperature (120–150ºC). It has been found in general with aliphatic
esters, xanthates or amine oxide which could form either a Z or E-alkene on pyrolysis that the more stable E
isomers is formed in larger amount. There is syn elimination therefore the threo isomer of the amine oxide gives
the Z-alkene while the erythro isomer gives the E-alkene.

CH3CH2CHCH3 CH3CH=CHCH3 + CH3CH2CH=CH2
Z = 12% 67%
O N(CH3)2 E = 21%

Mechanism:
O
N R R3 OH

R3 + N
H Ei
R1 R2
R R2
R1
EXAMPLES

N m-CPBA
O + N
rt, 100% CN
(i) O
OH
CN

N(CH3)2 
(ii) N(CH3)2

O
Named Reactions 199

H
H
i-Pr
100–180ºC
(iii) Me NMe2 Me i-Pr + Me i-Pr
H
H H O
65 % 35 %

H
H
i-Pr
H 90–160ºC
(iv) Me Me i-Pr
H
H NMe2
O

6.8. Crossed Cannizzaro Reaction

Reaction between different aldehyde
PhCHO + HCHO Conc. PhCH2OH + H COO–
NaOH

1. When formaldehyde undergoes a cannizzaro reaction with other aldehyde without a -H, then it is observed
that the formaldehyde is oxidised and other is reduced. This is because the nucleophilic attack occurs on
formaldehyde much easily than on any other aldehyde.
CHO CH2OH
O
NaOH
+ C H + HCOO
H
OCH3 OCH3
2. When HCHO reacts with other aldehyde with -H then first the cross aldol reaction takes place followed by
cross-cannizzaro reaction.
CH3 O CH2OH CH2OH
crossed OH–
CH CH + HCHO (H3C)2C (H3C)2C + HCOO
Aldol HCHO
H3C CHO CH2OH
Crossed Cannizzaro
Example:
CH2OH CH2OH
HCHO
(i) CH3 C CHO CH3 C CH2OH + HCOO
CH2OH CH2OH

CH2OH CH2OH
(ii) CH3CHO 3HCHO HCHO
CH2OH C CHO CH2OH C CH2OH + HCOO
CH2OH CH2OH
Named Reactions 200

CHO NaOH CH2 OH COO

(iii) 2 +
 COO
COOH COO
Intramolecular Cannizaro Reaction: Dialdehyde and-keto aldehyde undergo suitable I.C.R.

O O OH
OH– O HO OH O
H C C O H C C O Proton transfer
H C C O H C C O
Glyoxal H
H H H
CHO
rate = K OH 2nd order reaction
CHO
Hence, intramolecular cannizzaro is a second order reaction.
Normal Cannizzaro : 3rd Order Reaction: Cannizaro in strongly basic medium 4th order
Internal cannizaro - 2nd order

O OH
OH
Ph C CHO Ph C C O
O H
OH O O OH
proton transfer
Ph C C O Ph C C O
H H
H– ions come from aldehyde

6.9. Dakin Reaction

Aromatic carbonyl compounds having a hydroxy or amino group in either ortho or para position can be
converted to phenols on treatment with alkaline hydrogen peroxide.
CHO OH
OH OH
H2O2/OH–
+ HCOO

Mechanism:

O O O
O H
OH O C OH
C H O C H
O
H OH
OH OH OH
HOO OH

OH O
OH O OH
HCOO + H C OH +
Named Reactions 201
Examples:
O CH3
C OH

H2O2/OH–
(i) + CH3COO

NH2 NH2

C OH

H2O2/OH–
(ii) + C6H5COO

OH OH
6.10. Darzens Reaction
The Darzens reaction is the condensation of a carbonyl compound with an   haloester having atleast one
 -hydrogen in the presence of a base to form an ,   epoxy ester..
O O O
KO t-Bu R' CO2R'"
+ X
R R' OR'" t-BuOH R R"
R'
Mechanism: The first step in this reaction is addition of enolate of the   haloester to the carbonyl compound.
After this alkoxide oxygen formed in the addition does nucleophilic attack, displacing the halide and forming
,   epoxy ester(also called glycidic ester)
O O O O
O O
R
C
R R HC OC2H5 R2C CH OC2H5 C C OC2H5
R H
Cl Cl
O O O O
O
Cl OtBu Cl Cl
OEt Cl OEt O OEt
-tBuOH OEt syn
H H Cl
H
+
O O
Cl
OEt
anti
Cl
In the subsequent step, an intramolecular SN2 reaction form the epoxide.
O O O O
O OEt
– Cl–
OEt CO2Et
anti trans
Cl Cl

O
O
O OEt
O O – Cl–
CO2Et
Cl cis
OEt
syn Cl
Named Reactions 202

PROBLEMS

O
CO2C2H5
KOC(Me)3
1. O + ClCH2CO2C2H5
H
O
KOC(Me)3 H CO2C2H5
2. PhHC O + PhCHCO2C2H5
Ph Ph 75%
Cl
O O O
H3C CO2C2H5 Ph CO2C2H5
KOC(Me)3
PhCCH3 + ClCHCO2C2H5 +
3. Ph H H3C H

(1:1 mixture of isomers)

O
1. LiHMDS H3C CO2C2H5
4. CH3CH2CHCO2C2H5
2. O
Br Ph CH2CH3
C
H3C Ph

6.11. Dienone-Phenol rearrangement:

Acid-promoted rearrengement of 4, 4 disubstituted cyclohexadienones to 3, 4-disubstituted phenols.
O OH

H+

R
R R
R
Mechanism:

O H O OH OH

H+ 1, 2 alkyl –H+
H
shift
H R
R R R
R R R
R
EXAMPLES

O O

O
O
50% aq. H2SO4

(i) reflux, 80%

HO
O