Ullmann reaction

ullmann reaction

1. ULLMANN REACTION

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 CONTENTS

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. D iphenyl amines, diphenyl ethers and diphenyls can be synthesised . This is the first transition metal mediated coupling reaction for the formation of aryl– aryl bond. ULLMANN REACTION Introduction

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. ULLMANN REACTION Introduction

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 ULLMANN REACTION Introduction

6. ULLMANN REACTION Introduction

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. ULLMANN REACTION 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 ULLMANN REACTION Free radical mechanism

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 ULLMANN REACTION Ionic mechanism

10. A. Synthesis of biaryls and polyaryls a. Symmetrical biaryls ULLMANN REACTION Applications

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 . ULLMANN REACTION Applications

12. c . Polyaryl hydrocarbons: ULLMANN REACTION Applications

13. B. Synthesis of diarylamines : An arylamine and an arylhalide are refluxed in the presence of anhydrous potassium carbonate and copper powder . ULLMANN REACTION Applications

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 . ULLMANN REACTION Applications

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. ULLMANN REACTION Applications

16. ULLMANN REACTION Applications D. Gossypol synthesis:

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 ULLMANN REACTION Applications

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. REFERENCES: