| 摘要 |
#CMT# #/CMT# A method for the preparation of fluorinated sulfanylamides and sulfinamidines, involves the reaction of dialkylaminosulfur trifluoride with a perfluoroalkyl-trialkyl-silane in presence of a tert. amine to give a perfluoroalkyl-difluorosulfanyl-amine, followed by reaction with a prim. amine in presence of a tert. amine. #CMT# : #/CMT# A method (M1) for the preparation of sulfanylamides of formula R 1-NH-S-R 2 (I) and sulfinamidines of formula R 1-N=S(R 2)-N(R 3)R 4 (II), involves (a) condensation between compounds of formula R 2-Si(R 5)(R 6)R 7 (IV) and S(F) 3-N(R 3)R 4 (V) in organic solvent in presence of a tert. amine to give compounds of formula S(F) 2(R 2)-N(R 3)R 4 (III), (b) condensation of (III) with amines of formula R 1NH 2 in organic solvent in presence of a tert. amine to give (I) and/or (II), and possibly (c) conversion of (II) or the mixture of (I) and (II) in organic solvent in presence of an acid to give (I). R 1aryl, heteroaryl, alkyl, cycloalkyl, heterocycloalkyl, -SO 2-aryl,-SO 2-heteroaryl, -SO 2-fluoroalkyl, -COO-aryl, -COO-heteroaryl or -COO-alkyl (all optionally substituted except for -SO 2-fluoroalkyl); R 2perfluoroalkyl or difluoromethylene substituted with -S-aryl, -S-heteroaryl or optionally substituted benzoxazol-2-yl; R 3, R 4alkyl, alkoxyalkyl or cycloalkyl, or R 3 plus R 4 plus the linking nitrogen may form an optionally unsaturated 3- to 7-membered heterocycle which may also contain another hetero-atom (e.g. piperidinyl, pyrrolidinyl or morpholinyl); R 5, R 6, R 7optionally substituted alkyl or aryl . Independent claims are also included for (1) a method (M2) for the preparation of compounds of formula R 1R 0N-S-R 2 (Ia) by the alkylation of (I) with an alkylating agent of formula R 0X or R 0OSO 2R in an aprotic polar solvent in presence of a base (2) a method (M3) for the production of (I) by reacting (II) with an organic or mineral acid at a temperature between 0[deg] C and the boiling point of the solvent (3) compounds of formula (I), (II), (III) and (Ia) . R 0optionally substituted alkyl, alkenyl or alkynyl; X : halogen; R : optionally substituted alkyl or aryl . #CMT#USE : #/CMT# Sulfanylamides (I) and sulfinamidines (II) obtained by this method (and N-alkylated derivatives of (I)) are used as substitutes for bioactive molecules containing hydrophobic fluoroalkyl, fluoroalkoxy, fluoroalkylsulfanyl or fluoroalkylsulfonyl groups such as trifluoromethyl, trifluoromethoxy, trifluoromethylsulfanyl or trifluoromethylsulfonyl, by replacing these groups with fluorinated sulfanylamido or sulfinamidino groups (claimed). Also claimed is the use of (I) in which the sulfanylamido group is attached to an arylsulfonyl, heteroarylsulfonyl, fluoroalkylsulfonyl, alkoxycarbonyl, aryloxycarbonyl or heteroaryloxycarbonyl group as substitutes for bioactive molecules with carboxylic acid groups, by replacing the carboxylic acid group with a fluorinated sulfanylamidosulfonyl or sulfanylamidocarboxy group. Also claimed is the use of certain N-alkylated derivatives (Ia) (see above; with a perfluoroalkyl group attached to sulfur) for the perfluoroalkylsulfanylation of aryl, heteroaryl, alkenyl or alkynyl groups. These compounds are therefore useful in agrochemical or pharmaceutical applications as substitutes for the above types of bioactive molecules. #CMT#ADVANTAGE : #/CMT# Enables the preparation of fluorinated sulfanylamides and sulfinamidines. #CMT#ORGANIC CHEMISTRY : #/CMT# Preferred Methods: Compounds (III) are obtained by reaction of (IV) and (V) at -40 to +40[deg] C in a non-polar solvent, preferably dichloromethane, in presence of triethylamine, N,N-di-isopropylethylamine, pyridine or 2,6-lutidine. #CMT#DEFINITIONS : #/CMT# Preferred Definitions: R 1aryl (optionally substituted with halogen, alkyl, alkoxy, aryl, heteroaryl, alkenyl, alkynyl, fluoroalkyl, fluoroalkoxy, -S-fluoroalkyl, CN, nitro, heterocycloalkyl, -NR aR b, -NR aCOR b, -NR aCOOR c, -OSO 2R c, -CONR aR b, -COR b or -COOR c), heteroaryl (optionally substituted with halogen, alkyl, alkoxy, fluoroalkyl, fluoroalkoxy, CN, -NR aR b, -COR b or -COOR c), alkyl (optionally substituted with halogen, (hetero)aryl, heterocycloalkyl, alkoxy, -S-alkyl, fluoroalkyl, fluoroalkoxy, CN, nitro, -COOR c, -CONR aR b, -NR aR b, -NR aCOR b, -NR aCOOR c, -NR cCONR aR b or -NR aSO 2R c), -SO 2-aryl or -SO 2-heteroaryl (both optionally substituted with halogen, alkyl, alkoxy, fluoroalkyl, fluoroalkoxy, CN, nitro, -NR aR b, -COR b or -COOR c), -SO 2-fluoroalkyl, or -COO-alkyl (optionally substituted with F, aryl, heteroaryl, heterocycloalkyl, alkoxy, -S-alkyl, fluoroalkyl, fluoroalkoxy, CN, nitro, -COOR c, -CONR aR b, -NR aR b, -NR aCOR b, -NR aCOOR c, -NR cCONR aR b or -NR aSO 2R c); R a, R bH, 1-4C alkyl, 1-4C fluoroalkyl, cycloalkyl, aryl or heteroaryl (all optionally substituted), or heterocycloalkyl, or R a plus R b plus the linking nitrogen may form a 3- to 7-membered heterocycle (optionally unsaturated, optionally with another hetero-atom); R cas for R a, excepting H; R 21-2C perfluoroalkyl; R 3, R 4alkyl or oxyalkyl, or R 3 plus R 4 plus the linking N may form a morpholine group; R 5, R 6, R 7methyl . #CMT#EXAMPLE : #/CMT# A solution of 0.13 g N,N-di-isopropylethylamine in 2 ml dichloromethane (DCM) was treated at -20[deg] C with 0.135 ml diethylaminosulfur trifluoride DAST, stirred for 10 minutes at -20[deg] C, treated with 0.15 ml trifluoromethyl-trimethyl-silane and stirred for 1 hour at -20[deg] C to give N-(difluoro-(trifluoromethyl)-lambda 4>-sulfanyl)-N,N-diethylamine in quantitative yield (characterised by 19>F-NMR analysis). The unprocessed reaction mixture was treated at -20[deg] C with 0.091 ml aniline, stirred at room temperature (RT) for 12 hours and worked up by washing with 6% aqueous sodium bicarbonate solution, evaporation under reduced pressure and chromatography on silica (elution with pentane/acetone, 60/1), to give 0.156 g (81%) N-(trifluoromethylthio)-aniline (characterised by LC/MS and 1>H-NMR analysis). |
