Diazo coupling, formylation,carboxylation

Diazo-coupling
Formylation
Gattermann Reaction
Carboxylation
Kolbe-Schmitt Reaction

1. Topic:
ØDiazo-coupling
Ø Formylation
ØCarboxylation

2. qDevelopment of amines into diazonium salts as reagents for nucleophilic aromatic
substitution by S
N1 mechanism with loss of nitrogen
qElectrophilic aromatic substitution without the loss of nitrogen leads to important azo dyes
qTreatment of the amine with nitrous acid at 0 °C gives diazonium salt
Diazo-coupling

3. qDiazonium salts are good electrophiles for activated aromatic rings, amines and phenols
qDiazotization of salt of sulfanilic acid gives inner salt, combines with N,N-dimethylaniline to
form water-soluble dye, methyl orange

4. qElectrophilic substitution, occurring in para position on activated hindered dialkylamine
qNucleophilic attack occur on end nitrogen atom of diazonium salt to avoid forming
pentavalent nitrogen

5. Gattermann Reaction (Formylation)
qUseful in preparing aldehydes.
qUse Protonated hydrogen cyanide
qImine intermediate, ArCH=NH, hydrolyzed to aldehyde
qLewis acid need not so strong, zinc chloride often used
qWith less reactive systems, AlCl
3 needed
qZinc chloride conveniently generated from zinc cyanide, and HCl
•Generating necessary HCN
qAlkyl cyanide RCN use in place of HCN, useful way of preparing ketones from reactive
aromatic species, do not react well under Friedel–Crafts conditions

6. qElectrophile involved R–CºNH+, R(C=NH)Cl, analogue of acyl chloride, RCOCl
qIn Gatterman reaction, imine intermediate
qThese reactions work when three hydroxyls on benzene ring

7. Carboxylation (Kolbe–Schmitt Reaction)
qPhenoxide ion is more reactive towards electrophilic attack than phenol
qReact with such weak electrophiles as carbon dioxide
qindustrially used to prepare salicylic acid, precursor in making aspirin

8. qO
–
substituent is ortho, para-directing, electrophilic substitution step with CO
2 gives mostly
ortho product
•Coordination between sodium ion and two oxygen atoms, one from phenoxide and one
from CO
2
•Electrophile effectively delivered to ortho position