Methyl trifluoromethyl sulfoxide

Bis(trifluoromethyl) sulfoxide has been prepared1 previously by the direct fluorination of bis(trifluoromethyl) sulfide at —78°C. in hexafluoroethane followed by hydrolysis of the bis(trifluoro-methyl)sulfur difluoride (difluorobis(trifluoromethyl)sulfur). This method suffers because elemental fluorine must be used, and the yields are low. 

E)-3-Arylidenethiochroman-4-oncs possess thioether and oi,[)-unsaturatcd ketone functionalities both of which are susceptible to oxidation by DMD. In fact, chemoselective oxidation at sulfur is observed with a separable mixture of the sulfoxide and sulfone being produced in >5 1 ratio. A similar situation holds for the related thioflavanones. Epoxidation of the alkenic double bond in the thiochromanone 1,1-dioxides alone can be achieved using methyl(trifluoromethyl)-dioxirane (Scheme 65) <1994T13113>. However, reaction of NaOCl with 3-arylidenethioflavanones gives the epoxide and subsequent oxidation with DMD then gives a mixture of the sulfoxide and sulfone <2003MRC193>. 

Organic fluorine compounds and methods for their preparation are the central topic of the next four procedures. Much of the synthetic versatility of methyl phenyl sulfone is embodied in FLUOROMETHYL PHENYL SULFONE and the fluoro Pummerer reaction of methyl phenyl sulfoxide with DAST is a key step in its preparation. The utility of this fluoromethyl sulfone in the preparation of fluoroalkenes Is demonstrated in a companion procedure for Z-[2-(FLUOROMETHYLENE) CYCLOHEXYL]BENZENE, a procedure with several prominent stereoselective features. Geminal difluoroalkenes are featured in the following procedure. (3,3 DIFLUOROALLYL)TRIMETHYLSILANE is prepared by a method in which the radical addition of dibromodifluoromethane to alkenes and the selective reduction of a-bromoalkylsilanes are key steps. A procedure for nucleophilic introduction of the trifluoromethyl group completes this set. The key reagent, (TRIFLUOROMETHYL)-TRIMETHYLSILANE is obtained by reductive coupling of TMS chloride and bromotrifluoromethane. Liberation of a CF3- equivalent with fluoride ion in the presence of cyclohexanone affords 1-TRIFLUOROMETHYL-1-CYCLOHEXANOL. 

The C—N o-bond of N-aryltrifluoroacetamides and the S—N triple bond to afford l-[2-(arylamino)aryl]trifluoroethanones and (2-arylamino)aryl trifluoromethyl sulfoxides, respectively (Equations 12.19 and 12.20) [25]. The presence of the CF3 moiety in the substrates proved to be crucial for these insertion reachons to occur moreover, the reactions were limited to secondary amides or sulfinamides. No insertion product was detected in the case of the tertiary amide N-methyl-N-phenyltrifluoroacetamide. 

A sulfoxide was obtained by oxidation of 8-[(4-trifluoromethylmercapto-phenyl)methoxy] derivative 358 with 36% H2O2 in AcOH (98MIP7) and by oxidation of l-[2-(4-thiomorfolin-l-yl)acetyl]-7-(3-methoxyphenyl)-A-methyl-A- [3,5-bis(trifluoromethyl)phenyl]ethyl -5-oxo-1,2,3,5-tetrahydro-pyrido[l,2,3-i/ ]quinoxaline-6-carboxamide with 3-chloroperbenzoic acid (01MIP12). A 7-[(4-fluorophenylsulfonyl)methyl] derivative was obtained by oxidation of a 7-[(4-fluorophenylsulfanyl)methyl]perhydropyrido[l,2-u] prazine with 3-chloroperbenzoic acid in CHCI3 (01EUP1074257). 

II Flubendiamide sulfoxide [3-iodo-N-(2-methanesulfinyl-l,l-dimethyl-ethyl)-N -[2-methyl-4-(l,2,2,2-tetrafluoro-l-trifluoromethyl-ethyl)-phenyl -phthalamide ... 

A soln. of 4-diloro-N-trifluoroacetylanthranilic acid and SOCl in dry benzene refluxed 12 hrs. 7-chloro-2-trifluoromethyl-4H-3,l-benzoxazin-4-one (Y 93%) dissolved with methyl 5-methoxy-2-methyl-2,3-dihydroindole-3-acetate in dimethyl sulfoxide, and heated 12 hrs. on a steam bath methyl l-(2-trifluoroacetamido-4-dilorobenzoyl)-5-methoxy-2-methyl-2,3-dihydroindole-3-acetate (Y 82%). F. e. s. D.R. Olson, W.J. Wheeler, and J.N. Wells, J. Med. Chem. 17, 167 (1974). 

Note 1,2-BC 1,2-dunethylethylene carbonate 1,3-DOL 1 -dioxolane AC acetonitrile A.N. acceptor number BC butylene carbonate BEC butyl ethyl carbonate BMC butyl methyl carbonate CF3-EC trifluoromethyl ethylene carbonate QEC chloroethylene carbonate DBC dibutyl carbonate DEC diethyl carbonate DEE 1,2-diethoxyethane DGM diethyleneglycol dimethyl ether DIPC di-isopropyl carbonate DMC dimethyl carbonate DME 1,2-dimethoxyethane DMSO dimethyl sulfoxide D.N. donor number DPC di-n-propyl carbonate EC ethylene carbonate EIPC ethyl isopropyl carbonate EMC ethyl methyl carbonate EPC ethyl propyl carbonate MeTHF 2-methyl tetrahydrofuran MIPC methyl isopropyl carbonate MFC methyl propyl carbonate PC propylene carbonate TEGM tetraethylene glycol dimethyl ether TGM triethylene glycol dimethyl ether TFIF tetrahydrofuran. 

---