229 Heteroatom Chemistry Volume 9, Number 2, 1998 Synthesis of 4-Fluororesorcinol and 4- Trifluoromethylresorcinol Jing-Jing Yang, Debao Su, Ashwani Vij*, Timothy L. Hubler†, Robert L. Kirchmeier, and Jean’ne M. Shreeve* Department of Chemistry, University of Idaho, Moscow, ID 83844-2343 Received 6 June 1997; revised 4 August 1997 ABSTRACT Less expensive, safer, and easily scaled-up methods for the synthesis of 4-fluororesorcinol and 4-trifluorome- thylresorcinol have been established, including two methods to give the former compound. One involves the reaction of Selectfluor reagent with 1,3-dimeth- oxybenzene to give 2,4-dimethoxy-1-fluorobenzene fol- lowed by hydrolysis to give 4-fluororesorcinol. The overall yield of this two-step reaction is 54%. In the second case, when Selectfluor reagent is reacted di- rectly with resorcinol, under the best reaction condi- tions, 4-fluororesorcinol is obtained in 66% yield. It is, however, very difficult to separate the starting ma- terial from the mono- and difluororesorcinol products. Consequently, the two-step method is the method of choice to prepare 4-fluororesorcinol. The trifluoro- methyl group was incorporated into 2,4-dimethoxy-1- iodobenzene to form 1,3-dimethoxy-4-trifluoromethyl- benzene followed by mild hydrolysis to give 4-trifluo- romethylresorcinol.  1998 John Wiley & Sons, Inc. Heteroatom Chem 9:229–239, 1998 INTRODUCTION The introduction of the fluoro or trifluoromethyl group into organic molecules has recently been the Dedicated to Prof. William E. McEwen on the occasion of his seventy-fifth birthday. *To whom correspondence should be addressed. †Pacific Northwest National Laboratory, P.O. Box 999 MSIN K8-93, Richland, WA 99352  1998 John Wiley & Sons, Inc. CCC 1042-7163/98/020229-11 subject of increasing research activity. In particular, the replacement of hydrogen by fluorine or trifluo- romethyl groups in aromatic systems confers in- creased lipophilicity and acidity and modified hy- drogen bonding properties that often lead to dramatic changes in their bioactivities. This has re- sulted in interest in the development of cost-effective and convenient routes to fluorinated or trifluoro- methylated aromatic molecules. Recently, several advances in organofluorine chemistry have been translated into products of medicinal importance be- cause of the physiochemical properties the F atom imparts to these products [1]. In this article, we de- scribe our work concerning the synthesis of 4-fluo- roresorcinol and 4-trifluoromethylresorcinol. 4- Fluororesorcinol and 4-trifluoromethylresorcinol are useful for the preparation of polyfluorinated ion- exchange resins [2a–f]. There is much interest in the biochemistry of other fluorinated catechols and their interactions with chlorocatechol dioxygenase [3a]. Fluorinated catechols have also been used as build- ing blocks for the incorporation of 18 F into com- pounds useful as biologically active tracers [3b]. RESULTS AND DISCUSSION Although electrophilic fluorination of aromatic com- pounds has been studied over many years [4a], there are only a few reported routes to 4-fluororesorcinol (1) using this technique. In 1986, Patrick reported the synthesis of this compound by reacting cesium fluoroxysulfate (CsSO 4 F) with an activated aromatic system [4b]. Boron trifluoride was employed to cat- alyze the reaction between CsSO 4 F and resorcinol