Synthesis 2008(12): 1867-1878  
DOI: 10.1055/s-2008-1067080
PAPER
© Georg Thieme Verlag Stuttgart · New York

Aromatization via a Dibromination-Double Dehydrobromination Sequence: A Facile and Convenient Synthetic Route to 2,6-Bis(trifluoroacetyl)phenols [1]

Dmitri V. Sevenard*a,2, Olesya Kazakovaa, Ralf-Matthias Schotha, Enno Lorka, Dmitri L. Chizhovb, Jörn Poveleita, Gerd-Volker Röschenthaler*a
a Institute of Inorganic & Physical Chemistry, University of Bremen, Leobener Str., 28334 Bremen, Germany
Fax: +49(421)2208409; e-Mail: [email protected]; Fax: +49(421)2184267; e-Mail: [email protected];
b Institute of Organic Synthesis, Russian Academy of Sciences Ural Branch , S. Kovalevskoy Str. 22, GSP-147, 620041 Ekaterinburg, Russian Federation
Further Information

Publication History

Received 21 November 2007
Publication Date:
16 May 2008 (online)

Abstract

An efficient and reliable method to synthesize 2,6-bis(trifluoroacetyl)phenols bearing various substituents in the 4-position was developed. These valuable fluorinated building blocks were obtained from the corresponding cyclohexanones in a facile and convenient procedure, demonstrated to be superior to the traditional approaches. The application of this methodology to cyclohexane-1,4-dione opened access to 2,5-bis(polyfluoroacyl)-1,4-hydroquinones. Structural peculiarities of the obtained phenols as well as their 1,3-dicarbonyl or 1,3,5-tricarbonyl precursors are discussed on the basis of multinuclear NMR spectroscopy.

1

This work was presented in part at the 18th International Symposium on Fluorine Chemistry, Bremen, Germany, 30 July-4 August 2006.

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1

This work was presented in part at the 18th International Symposium on Fluorine Chemistry, Bremen, Germany, 30 July-4 August 2006.

2

Present address: Hansa Fine Chemicals GmbH, BITZ, Fahrenheit Str. 1, 28359 Bremen, Germany.

13

For the synthesis of related bridged dibromoketones from fluorinated 1,3,5-triketones, as well as for the stereochemis-try of 4, see ref. 11.

14

2,4-Dibromo-6-(trifluoroacetyl)phenol and 4-bromophenol 3j and its monohydrate could be identified (see experimental procedure), whereas the targeted acid 3g was not detected at all.

28

For freshly prepared CDCl3 (3d,h,i,j and 5a,c,f,k), acetone-d 6, or THF (5g) solns. It is notable that if the CDCl3 soln of 5c is maintained at r.t. for 20 h, the [bis-enol]/[F]/[G] molar ratio changes from 53:24:23 to 89:6:5 (by NMR spectroscopy). Contact with silica gel leads to hydration of phenols 3. When a mixture of 3j is stirred with silica gel in CHCl3, the concentration of the hydrate form increases from 11% to 70% after 14 h at r.t. Dehydration can be achieved if the substance is maintained in anhyd CHCl3: for 3j the hydrate content changed from 70% to 11% after 7 d at r.t. The use of 4-Å MS accelerates dehydration. In this case, the content of the hydrate form decreases to 7% after 17 h at r.t. (by 19F NMR). Anhyd MgSO4 appeared to be inefficient.