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.
Key words
fluorinated compounds - arenes - ketones - aromatization - phenols
References 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.
3a Welch JT.
Tetrahedron
1987,
43:
3123
3b Lin P.
Jiang J.
Tetrahedron
2000,
56:
3635
3c Welch JT.
Eswarakrishnan S.
Fluorine in Bioorganic Chemistry
Wiley;
New York:
1991.
3d Organofluorine Chemistry - Principles and Commercial Applications
Banks RE.
Smart BE.
Tatlow JC.
Plenum;
New York:
1994.
3e Bégué J.-P.
Bonnet-Delpon D.
Chimie bioorganique et médicinale du fluor
CNRS Editions;
Paris:
2005.
4a Hiyama T.
Organofluorine Compounds. Chemistry and Application
Springer;
Berlin:
2000.
4b Kirsch P.
Modern Fluoroorganic Chemistry, Synthesis, Reactivity, Applications
Wiley-VCH;
Weinheim:
2004.
4c Chambers RD.
Fluorine in Organic Chemistry
Blackwell;
Oxford:
2004.
5 Mandal SK.
Nag K.
J. Chem. Soc., Dalton Trans.
1983,
2429
6 Schoth R.-M.
PhD Thesis
University of Bremen;
Germany:
1996.
7 Ansong O.
Antoine MD.
Nwokogu GC.
Hergenrother PM.
J. Org. Chem.
1994,
59:
2506
8a Prelog V.
Metzler O.
Jeger O.
Helv. Chim. Acta
1947,
30:
675
8b Jones ECS.
Kenner J.
J. Chem. Soc.
1931,
1842
8c Bertz SH.
Synthesis
1980,
708
8d Nishiwaki N.
Tohda Y.
Ariga M.
Synthesis
1997,
1277
9 Sevenard DV.
Kazakova O.
Chizhov DL.
Röschenthaler G.-V.
J. Fluorine Chem.
2006,
127:
983
10a Openshaw HT.
Robinson R.
J. Chem. Soc.
1946,
912
10b Coumbarides GS.
Dingjan M.
Eames J.
Weerasooriya N.
J. Chem. Res., Synop.
2000,
328
11 Sevenard DV.
Kazakova O.
Chizhov DL.
Yachevskii DS.
Lork E.
Poveleit J.
Charushin VN.
Röschenthaler G.-V.
Helv. Chim. Acta
2007,
90:
369
12a Sevenard DV.
Khomutov OG.
Kodess MI.
Pashkevich KI.
Russ. Chem. Bull.
1999,
48:
400
12b Chizhov DL.
Pashkevich KI.
Röschenthaler G.-V.
J. Fluorine Chem.
2003,
123:
267
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.
15 Archer S.
Perianayagam C.
J. Med. Chem.
1979,
22:
306
16 Duan J.
Zhang LH.
Dolbier WR.
Synlett
1999,
1245
17 Kirsch P.
Reiffenrath V.
Bremer M.
Synlett
1999,
389
18 Linderman RJ.
Jamois EA.
J. Fluorine Chem.
1991,
53:
79
19a Herrman F.
Liebigs Ann. Chem.
1882,
211:
306
19b Guha PC.
Chem. Ber.
1939,
72:
1359
19c Bagrov FV.
Bagrov DF.
Russ. J. Org. Chem. (Engl. Transl.)
1994,
30:
637
20 The Chemistry of Enols
Rappoport Z.
Wiley;
Chichester:
1990.
21 Koelle U.
Forsén S.
Acta Chem. Scand., Ser. A
1974,
28:
531
22 Sevenard DV.
Kazakova O.
Lork E.
Dülcks T.
Chizhov DL.
Röschenthaler G.-V.
J. Mol. Struct.
2007,
846:
87
23a Koltsov AI.
Kheifets GM.
Russ. Chem. Rev. (Engl. Transl.)
1971,
40:
773
23b Emsley J.
Struct. Bonding
1984,
57:
147
23c Koltsov AI.
J. Mol. Struct.
1998,
444:
1
24 Sosnovskikh VY.
Russ. Chem. Bull.
2001,
1223
25 Neyland OY.
Stradyn’ YaP.
Silin’sh EA.
Balode DR.
Valtere SP.
Kadysh VP.
Kalnin’ SV.
Kampar VE.
Mazheyka IB.
Taure LF.
Stroenie i Tautomernye Prevrashcheniya β-Dikarbonil’nykh Soedineniy (in Russian)
Zinatne;
Riga:
1977.
26 Wustrow D.
Belliotti T.
Glase S.
Kesten SR.
Johnson D.
Colbry N.
Rubin R.
Blackburn A.
Akunne H.
Corbin A.
Davis MD.
Georgic L.
Whetzel S.
Zoski K.
Heffner T.
Pugsley T.
Wise L.
J. Med. Chem.
1998,
41:
760
27 Kohn M.
Segel A.
Monatsh. Chem.
1925,
46:
661
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 19 F NMR). Anhyd MgSO4 appeared to be inefficient.
29 Okada Y.
Yokozava M.
Akiba M.
Oishi K.
Okawa K.
Akeboshi T.
Kawamura Y.
Inokuma S.
Nakamura Y.
Nishimura J.
Org. Biomol. Chem.
2003,
1:
2506
