2. Introduction
Mechanism
Free radical mechanism
Ionic mechanism
Applications
Synthesis of biaryls and polyaryls
Synthesis of diaryl amines
Synthesis of diaryl ether
Gossypol synthesis
Indole synthesis
3. In 1901, Ullmann reported a useful technique
for the formation of a new C–C bond between
two aryls by the condensation of two
molecules of aromatic halide in the presence
of finely divided copper which is known as
Ullmann reaction. Diphenyl amines, diphenyl
ethers and diphenyls can be synthesised.
This is the first transition metal mediated
coupling reaction for the formation of aryl–
aryl bond.
4. The reaction involves the condensation of aryl
halides in the presence of finely divided
copper or copper bronze at an elevated
temperature (100-350 C) to yield diaryl
derivatives. Thus, iodobenzene in
nitrobenzene when heated in the presence of
copper powder gives diphenyl in 80% yield.
Alternatively, the reactants may be heated in
a sealed tube.
5. Aryl Iodides are good for this reaction but aryl bromides
and chlorides also react when electronegative
substituents, which activate the halogen, like nitro,ester
etc. are present at ortho and para position. Order of
reactivity is
ArI >ArBr>ArCl
6.
7. The mechanism for the Ullmann
reaction is not known with
certainty but there are two
proposed popular mechanisms
1. Free radical mechanism.
2. Ionic mechanism.
8. According to free radical mechanism, the
copper generates an aryl radical by a single
electron transfer (SET) from copper metal to
the alkyl halide. Two aryl radicals then react
to form the final biaryl products
9. According to the ionic mechanism, an aryl copper
intermediate is formed. This mechanism begins with
the oxidative addition of the copper to the aryl halide
followed by a single electron transfer to form an
organocuprate reagent .This organocuprate performs
another oxidative addition on an aryl halide forms
biaryl copper halide complex which after reductive
elimination results in the final biaryl product
10. A. Synthesis of biaryls and polyaryls
a. Symmetrical biaryls
11. b. Unsymmetrical diaryls:
With a mixture of two different aryl halides, three
products are obtained which has poor synthetic value
for the yield of the desired product is low and
difficult to isolate. In some cases, however,the
unsymmetrical product is only formed, e.g.
13. B. Synthesis of diarylamines:
An arylamine and an arylhalide are refluxed in the
presence of anhydrous potassium carbonate and
copper powder.
14. C. Synthesis of diaryl ether:
A phenolic compound and an aryl halide are refluxed
in the presence of potassium hydroxide or K2CO3
and copper. The reaction has been employed in the
synthesis of thyroxine.
15. D. Gossypol synthesis:
Meyers and Willemsen developed the first asymmetric
synthesis of (S)-(+)-gossypol via a traditional
Ullmann coupling. Heating a 40 % solution of
bromonaphthyl oxazoline derivative in freshly
distilled DMF and activated copper at reflux for 1 h
gave the binaphthyl derivative by Ullmann coupling in
80 % yield as a 17:1 diastereoisomeric mixture. This
is the key step for the total synthesis of (S)-(+)-
gossypol.
Gossypol has antimalarial activity and it is used in
china as oral male contraceptive.
17. E. Indole synthesis
Banwell and co-workers developed the synthesis of
indoles via Pd(0)-mediated Ullmann cross-coupling
of o-halonitrobenzene and with arrange of a-halo-
enones followed by reductive cyclization
18. Sanyal,S.N.;Reactions, Rearrangements and
Reaents,Bharati bhawan P&D, pg-197-181
Mondal,S.; Recent advancement of Ullmann-
type coupling reactions in the formation of C–
C bond, ChemTexts (2016) 2:17.
