Deoxyfluorination of acyl fluorides to trifluoromethyl compounds
with Fluolead
Norimichi Saito and Southida Nachampassak of UBE Industries introduce a new method for deoxyfluorination
Fluolead
*
( 4-tert-butyl-2,6- dimethylphenylsulfur trifluoride , Figure 1 ) is UBE Industries ’ novel nucleophilic fluorinating reagent . This is based on alkyl-substituted benzene and SF 3 and has been used in deoxyfluorination reactions and , recently , as a reagent for producing trifluoromethyl ( CF 3
). It is a white , crystalline solid and has good flowability , making it easy to handle .
Development of Fluolead
Diethyl amino sulfur trifluoride ( DAST , Figure 1 ) is currently the commonest deoxy-fluorinating reagent for use in reactions where an oxygen atom is substituted by a fluorine . By these means , alcohols are converted to single fluorine compounds , ketones and aldehydes to geminal difluoride and carboxylic acids to CF 3
. The structure of DAST is a synthon of inorganic SF 4
, with one fluorine replaced by diethylamine . Handling it in the laboratory poses many difficulties . It is highly moisturesensitive and fumes immediately appear when the bottle is opened . In addition , due to its lack of the thermal stability , applications for DAST are limited to the laboratory and are difficult to expand to commercial-scale production . The thermal decomposition process begins with the disassociation of the N-S bond , which starts a chain decomposition reaction and causes an explosion . A more thermally stable and easier to handle fluorinating agent has long been sought . To address this , Dr
Figure 1 – Development of Fluolead
Teruo Umemoto , president of IM & T Research , firstly focused on the weakness of N-S binding energy to find a new fluorinating reagent that has a higher binding energy than DAST and can provide good thermal stability . The focus was on the C-S bond , because its binding energy is 714 kJ / mol . Fluolead has one tert-butyl group and two dimethyl groups on its benzene ring . This shows very good fluorination , ability , especially deoxofluorination , with thermal stability up to 170 ° C , and the hindered structure gives enough stability against moisture to handle it in the open air . In addition , no fumes appear when Fluolead is exposed to water . Since the product is solid , weighing conditions for the reaction are easier . Fluolead requires only one step for deoxo-fluorination , and it has a higher selectivity and a lower risk than older generation reagents . Thus , it has been introduced to the market and is now available at commercial scale .
Comparison of reagents
Fluolead is also a nucleophilic fluorination reagent that is able to ‘ deoxy-fluorinate ’ ketones ( non-enol form ) and carboxylic acids . Figure 3 shows some examples . The first is a ketone ( enol form ) that reacts with Fluolead and nHF-Py , also known Olah ’ s reagent ( a mixture of 70 % hydrogen fluoride ( HF ) and 30 % pyridine ), at room temperature and gives the corresponding geminal difluoro-compounds in high ( 81 %) yield . Normally , this kind of enol-ketone gives an undesired side product ( B ), but the reaction proceeds with very good selectivity compared to other fluorinating reagents , such as DAST , Deoxo-Fluor or XtalFluor-E .
58 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981