Lecture On:

Important Name Reactions

By: Dr. Nishat Fatima(Assistant Professor)

Department of ChemistryShia P.G.College, Lucknow

E-Lecture Content: Organic ChemistryFor the students of B.Sc. IInd Year, IVth Semester

as per Lucknow University syllabus

IMPORTANT NAME REACTIONS AS PER SYLLABUS

1. PINACOL- PINACOLONE REARRANGEMENT2. FRIES REARRANGEMENT3. CLAISEN REARRANGEMENT4. GATTERMANN SYNTHESIS5. HAUBEN HOESCH REATION6. LEADERER MANASSE REACTION 7. RIEMANN TIEMANN REACTION 8. BENZOIN CONDENSATION9. ALDOL CONDENSATION10. PERKIN CONDENSATION11. KNOEVENAGEL CONDENSATION12. WITTING REACTION13. MANNICH REACTION14. BAEYER VILLGGER OXIDATION OF KETONES15. CANNIZZACO REACTION16. MPV17. CLEMENSEN REDUCTION18. WOLFF KISHNER REDUCTION19. HVZ REACTION20. GABRIEL PHTHALIMIDE REACTION21. HOFFMANN BROMIDE REACTION22. AZO COUPLING

PINACOL- PINACOLONE REARRANGEMENT

1,2 Diols (Subsituted vicinal diols) such as 2,3 dimethyl-2,3 butanediol are calledpinacol. On treatment with mineral acid they undergo dehydration and rearrangementresulting to form tert.-butyl methyl ketone (pinacolone).

CH3 C

CH3

OH

C

CH3

OH

CH3H+

HEAT,-H2O

CH3 C

O

C

CH3

CH3

CH3

2,3- Dimethyl 2,3-butanediol 3,3-Dimethyl 1,2-butanone

(Pinacolone)(Pinacol)

FRIES REARRANGEMENTIn this reaction the phenolic ester is heated with anhyd. AlCI3, the phenyl groupmigrated to form phenolic oxygen to ortho & para positions giving a mixture of ortho& para Hydroxy Ketones.

CH3

O

C

OH

OOH

CCH3

O C

O

CH3

+

PHENYL ACETATE ORTHO HYDROXY ACETOPHENONE

PARA HYDROXY ACETOPHENONE

H+/ H2O(ii)

(i) Anhy AlCl3, Heat

CLAISEN REARRANGEMENTIn this rearrangement, when a allyl phenyl ether is heated alone or in an inert solvent(eg diphenyl ether) at 475 K it forms allyl phenols. Allyl group migrated to a orthoposition and if both ortho position are occupied then it goes to para position.

O CH2 CH CH2

473 K

OH

CH2 CH CH2

ALLYL PHENYL ETHER

ORTHO ALLYL PHENOL

473 K

ALLYL 2,6-DIMETHYL PHENYL ETHER

4, ALLYL - 2,6-DIMETHYL PHENO

O CH2 CH CH2CH3 CH3

CH3 CH3

OH

CH2 CH CH2

GATTERMANN ALDEHYDE SYNTHESISOR GATTERMANN FORMYLATION

When a phenol is heated with a mixture of hydrogen cyanide and HCl in the presence of anlyd AlCl3 it forms corresponding aldimine hydrochloride, which upon heating-boiling with water undergoes hydrolysis to give corresponding phenolic aldehyde.

OH

CHO

OH

CH=NH.HCl

OH

Phenol

p-hydroxybenzaldehyde

AldimineHydrochloride

H2O, BoilAnlyd+ HCN

AlCl3NH4Cl

HAUBEN HOESCH REACTION

Polyhydic phenol + aliphatic nitriles Polyhydroxy ketones

Polyhydic phenol react with aliphatic nitriles in the presence of anhydrous ZnCl2 or AlCl3 then acyl group is introduced to benzene ring at ortho position to hydroxyl group (-OH).

LEADERER MANASSE REACTION(Condensation with formaldehyde)

Phenol condence with aldehyde in the presence of acid or base catalyst to form orthoand para hydroxyl benzyl alcohols. The reaction does not stop here. The ortho andpara hydroxyl benzyl alcohols further condence with other phenols molecules to givea polymeric compound known as Bakelite.

By repetitive condensation reaction at all the available ortho and para position ofphenol (iii- vii) ultimately leads to the formation of BakeliteBakelite- Phenol formaldehyde resin , a highly cross linked polymer.

OH

H+ or OH-H

HC = O

CH2OH

OH OH

CH2OH para-hydroxy pheno

(Major)(II)

ortho-hydroxy phenol (minor)

(I)

OH

Phenol

LEADERER MANASSE REACTION

I + II HCHO

H+ or OH-

CH2OH

OH

CH2OH CH2OHCH2OH

OH

III

IV

OH

HO CH2 OH + HO CH2

OH

+

OH

CH2

OH

VII

VI

III + IV + V +VI + VIIHCHO

HO

CH2H2C CH2

OH

CH2 CH2 CH2

H OR

OH

BakelliteC6H5OH, H+,OH-

RIEMANN TIEMANN REACTION

When phenol is treated with chloroform in the presence of aqueous sodium orpotassium hydroxide at 340 K followed by hydrolysis it yields 2- hydroxybenzaldehyde (salicyldehyde) as major product along with small amount of p-hydroxy benzaldehyde

Mechanism- electrophilic subsitution reactionElectrophile- dichlorocarbene

OH

CHCl3(I) NaOH, 340 K

(ii) H3O

OH

CHO

OH

CHO(Minor)

(Salicyldehyde Major)

BENZOIN CONDENSATION

Aromatic aldehydes that do not contain α- hydrogen atom cannot undergo Aldolcondensation but they undergo self condensation in the presence of alc. KCN to formα- hydroxy ketones (benzion)

Mechanism: Kinetics of the reaction shows that Benzoin condensation is first order in cyanide ion and second order in benzaldehyde

C H

OAlk KCN

HeatC

O

C

OH

BenzoinBenzaldehyde

2

Mechanism

BENZOIN CONDENSATION

C6H5 - C + CN C6H5 C - H C6H5 C C6H5 C

OH

C=NC N

O

CNH

O

(Nucleophile)

C5H6 C

OH

CN

C

O

H

C6H5 C6H5 C

OH

H

C6H5C - C -C6H5

O

CN

OH

H

C6H5 C-C-C6H5

O OH

C C6H5

O

(Benzoin)

ALDOL CONDENSATIONIn this reaction two molecules of aldehyde or ketones (having α hydrogen/s)undergo self condensation in the presence of dilute alkali eg. Dil. NaOH, Ba(OH2),Na2CO3 etc. To form aldols (β- hydroxyaldehyde or β- hydroxyketone)

C OCH3

CH3

2 (Ba(OH)2 C

OH

CH3 CH2 CO CH3

CH3

AcetoneDiacetone mole 3-Hydroxy-4-methyl pentan-2-one

C OCH3

HCH2H CHO

dil NaOHCH3 C CH2 CHO

OH

H

Acetaldehyde (2 mole) Aldol(3-Hydroxybutanol)

PERKIN CONDENSATION

In this reaction the acid anhydride (containing α hydrogen) added to aromaticaldehyde in the presence of sodium salt of carboxylic acid from which the anhydridederived as the base, firstly it forms the condensation product which upon hydrolysisgives the corresponding α, β- unsaturated acid.

C6H5CH O OCH3CO

CH3CO CH3COONa, 453 K

-H2O

C6H5 CH CHCOO

CH3CO

C6H5CH CHCOOH

Benzaldehyde Acetic anhydride

Cinnamic acid

Condensation product

Acetic acid

CH3COOH

H2O,Boil

Hydrolysis

KNOEVENAGEL CONDENSATION

This reaction involves the condensation of an aromatic or aliphatic aldehyde with anactive methylene compound (eg. Malonic acid, malonic ester, acetoacetic ester,cyanoacetic esternitroalkanes etc.) in the presence of a base such as piperidine,pyridine to form α, β- unsaturated compounds.

C O H2CX

Y

Pyridine or

Piperidine, heat

C CX

YH2O

Aldehyde Active methylene compound

Condensation product

RCH O H2CCOCH3

COOC2H5

Pyridine, heatRCH C

COCH3

COOC2H5

H2O

Aliphatic oraromatic aldehyde

Ethyl acetoacetate Condensation product

WITTING REACTIONIn this reaction aldehyde and ketones react with each other in the presence ofphosphorus ylide (Witting reagent) to give a subsituted alkene.

•Phosphorus ylide: Alkylidenephosphoranes, (C6H5)3P=CRR’Where R and R’ may be H, Alkyl or Aryl group

C OR

R'C P(

R''

R'''

C6H5)3THF

CR

R'C

R''

R'''C6H5 3 P O

Carbonyl Compound

Subsituted alkene Triphenylphosphineoxide

A phosphorous ylide

C OH3C

H3CCH2 PC6H5 3

THF CH3 C

CH3

CH2

Acetone 2- methyl propene

C6H5 CH O THF3PC6H5CH2 C6H5 CH CH2

OP3C6H5

OP3C6H5

Benzaldehyde Styrene

MANNICH REACTION

In this reaction an active methylene compound (usually an enolizable ketone) reactwith formaldehyde and an amine (usually a sec amine) react with each other in thepresence of an acid to give a product which upon basification yields a β- aminocarbonyl compound.

C6H5 C

O

CH3 HCHO CH3 2NHHCl C6H5 C

O

CH2 CH2 NH CH3 2Cl

NaOH NaCl,

H2O

2CH3C6H5 C

O

CH2 CH2 N

Acetophenone(An enolizable ketone)

Dimethyl amine(sec amine)

A Mannich base(beta- dimethyl aminopropiophenone)

BAEYER VILLGGER OXIDATION OF KETONES

In this reaction conversion of acyclic ketones into esters and cyclic ketones intolactones carried out by the treatment of peracid (eg. perbenzoic acid, peracetic acid, m-chloroperbenzoic acid, trifloroperacetic acid etc.). Out of all the peracids,trifluoroperacid is most reactive because it is very good leaving group.

R C

O

R C6H5 C

O

O O H R C

O

OR C6H5 C

O

H

Ketone Perbenzoic acid Ester Benzoic acid

O

CF3 C

O

O O H

O

O

CF3COOH

Cyclohexanine Trifluoroperaceticacid

Caprolactone Trifluoroaceticacid

CANNIZZACO REACTION

In this reaction aldehydes which do not contain α hydrogen atom (eg. formaldehyde,benzaldehyde, trimethyl acetaldedyde etc.) undergo disproporation reaction (i.e.Self oxidation-reduction) in the presence of strong base (concentrated alkalisolution) to form equal amount of corresponding alcohols and carboxylic acids.

HCHO2 NaOH CH3OH HCOONa

Formaldehyde (50%) Methyl alcohol Sod. formate

C6H5OH

(50%)

NaOH C6H5CH2OH C6H5COONa

Benzyl alcohol Sod. benzoateBenzaldehyde

H C

O

C

O

OH NaOH HO CH2 C

O

ONa

COONa

COONa H2O2

Glyoxylic acid Sod. glycollate Sod. oxalate

2

2

MEERWEIN-PONNDORF-VERLEY REDUCTION (MPV)

This reduction is used for converting carbonyl group into alcohol. This reaction isreverse of Oppenauer oxidation. In this reduction ketone is heated with aluminiumisopropoxide in the presence of excess of isopropyl alcohol. Ketone is reduced tocorresponding alcohol and isopropyl alcohol is oxidised to acetone. This reduction ishighly selective method so very useful method for converting carbonyl compounds tounsaturated alcohols.

C OR

R'CHOH

CH3

CH3

Al OCH CH3 23 CHOH

R

R'C O

CH3

CH3

Ketone 20 Alcohol AcetoneIsopropyl Alcohol

CLEMENSEN REDUCTION

In this reduction aldehyde or ketones are reduced with the help of zinc amalgam andconc. HCl to the corresponding hydrocarbon.In this reaction the carbonyl group is reduced to methylene group to formhydrocarbon.This method works good for ketones but not for aldehydes and widely used forreduction of ketones that are sensitive to alkalies.

C

O

CH3

H4Zn-Hg/HCl

CH2

CH3

Acetophenone Ethyl benzene

H2O

WOLFF KISHNER REDUCTION

In this reduction aldehyde or ketone is heated with strong base (eg. KOH orpotassium tert. butoxide) and hydrazine (NH2NH2) in a high boiling solvent (eg.Ethylene glycol) at 453-473 K to give the corresponding hydrocarbon.This method is used for reduction of acid sensitive aldehyde or ketones.

COCH2CH3NH2 NH2 , KOH ,

HOCH2 CH2OH

453-473 KCH2CH2CH3

Propiophenone n-Propylbenzene

HELL-VOLHARD-ZELINSKY REACTION (HVZ)Or Halogination of carboxylic acid

In this reaction carboxylic acids except formic acid (it does not contain alkyl group)react with Cl2 or Br2 in the presence of red P to give the corresponding α- chloro orbromo acids.

CH3COOH

-HClClCH2COOH

Cl2, Red P Cl2, Red P

-HClCl2CHCOOH

Cl2, Red P

-HCl

Acetic acid Chloroacetic acid Dichloroacetic acid Trichloroacetic acid

Cl3CCOOH

GABRIEL PHTHALIMIDE REACTION

In this reaction phthlamide is converted into potassium salt on treatment with KOH then pot. Phthalamide on treatment with an alkyl or aryl halide forms N-subsitutedphthalamide, which finally hydrolysed (under pressure with 20% HCl) to produce phthalic acid and a primary amine.

C

O

C

O

NHKOH

C

O

C

O

NKRX

KX

C

O

C

O

NR

H+,H2O

C

O

C

O

OH

OH

Phthalic acid

Phthalamide Pot. salt of phthalamide

RNH2

Primaryamine

HOFFMANN BROMIDE REACTION

When primary amines are treated with bromine or chlorine in the aqueous alkali solution they are converted into amines, containing one carbon atom less than the original amide.

RCONH2 Br2 4KOH RNH2 K2CO3 2KBr 2 H2O

Amide Amine

CH3CONH2 H2O22KBrK2CO34KOHBr2 CH3NH2

Methyl amineAcetamide

AZO COUPLING

This reaction is an important reaction of diazonium salt. In this reaction diazoniumions (act as electrophile) react with aromatic compounds (containing strong e-releasing group such as –OH, NHR, NHR2 etc.) to form azo compounds containing

bond.N N

Where G is any electron releasing group

N NCl GH N N G H+

References

Organic chemistry by Dr. S.N. Dhawan

Organic chemistry by R. L. Madan

Organic chemistry by Y.R. Sharma